bluuebunny/crossref_metadata_2025 huggingface dataset:
ON THE URINE OF WOMEN UNDER NORMAL CONDITIONS, WITH SPECIAL REFERENCE TO THE PRESENCE OF CREATIN
Authors: Krause R. A.
Published: December 2014

1. Creatin is present in the urine of women immediately after menstruation; it may or may not be present during the intermenstrual period. In women creatin is therefore not an abnormal urinary constituent.

2. Creatin is present in the urine of women during pregnancy. So‐called “post‐partum creatinuria” is only a temporary increase in the creatin excretion which occurs throughout pregnancy.

3. After menstruation the distribution of the nitrogen in the urine is changed. There is an increase in the excretion of ammonia and of undetermined nitrogen, a decrease in the excretion of urea. A similar change takes place during pregnancy.

4. Observations on a bitch during the œstrous and anœstrous periods confirm the existence of a correlation between creatinuria and the female sexual cycle.
FURTHER OBSERVATIONS UPON THE COMPARATIVE ANATOMY AND PHYSIOLOGY OF THE PITUITARY BODY
Authors: Herring P. T.
Published: December 2014

The pituitary bodies of the classes of vertebrates examined show a remarkable resemblance to one another in the essential features of their structure. The pituitary body of the elasmobranch fishes forms a type peculiar to itself, its chief distinction being a negative one—the nonpossession of a nervous lobe. With this exception the vertebrate pituitary is composed of an epithelial or glandular lobe lying in close relationship with an evagination of the floor of the third ventricle of the brain, the wall of which is peculiarly modified to form a nervous lobe.
ON THE REFLEX NATURE OF APNŒA IN THE DUCK IN DIVING. II. REFLEX POSTURAL APNŒA
Authors: Huxley Frances M.
Published: December 2014

There is still a considerable amount of work to be done on the variations in posture which affect—and as to what degree they affect—the respiratory centre of the duck, and on the nature of the receptive elements which bring about these changes.

The results so far determined are as follows:—

1. A well‐marked reflex postural apnœa can be produced under the conditions brought about by extension or dorsi‐flexion of a duck's head and neck, when the animal lies upon its back.

2. Its value to the duck appears to be as a mechanism to aid it in resisting the inspiration of water when in the diving position. Apnœa, as well as other reflex phenomena associated with diving, can be readily produced by placing the duck in the diving position, quite apart from the presence of water. The appearance of the apnœa is not, however, as constant in this position as in 1.

3. The evidence also shows that the fact of extension or dorsi‐flexion of the neck plays a part in producing apnœa.

4. Breathing continues when the vertex of the duck's head faces upwards, and it stops when the vertex faces downwards.

5. Experiments made after having broken up the labyrinths indicate that their function upon respiration is twofold, causing it to continue in certain positions, e.g. vertex up, and stopping it in others, e.g. vertex down, and that after its destruction extension in all positions is generally capable of bringing about a pause in breathing.
OBSERVATIONS ON THE AURICULO‐VENTRICULAR JUNCTION OF THE MAMMALIAN HEART
Authors: Stanley Kent A. F.
Published: December 2014

The muscular connection between auricle and ventricle in the heart of man is not single and confined to the A.V. bundle, but it is multiple.

One point at which a muscular connection between auricle and ventricle exists is situated at the right margin of the heart.

The coordinated action of the chambers of the heart is to some extent dependent upon the integrity of muscular connections other than that which exists in the A.V. bundle.

It is proposed, for purposes of identification, to refer to the connection described as the “right lateral” connection.
EFFECTS OF LOWERING THE TEMPERATURE OF HOMOIOTHERMIC ANIMALS
Authors: Britton S. W.
Published: December 2014

1. In the process of lowering the temperature of homoiothermic animals there is a progressive paralysis of the central nervous system as indicated by the gradual disappearance of voluntary and reflex actions. In recovery a definite order of reappearance of reactions occurs at different deep rectal temperatures as follows :—

Knee jerk and micturition reflexes ............... 16°

Achilles‐thrust, and anal sphincter respiratory reflex ................ 17

Stepping reflex .......... 18

Shivering reflex .......... 19.5

Pinnae, vibrissae, flexion (of limb) and phonation reflexes ........ 20

Clawing and winking reflexes ................. 21.5

Head‐shake, corneal, sneezing and swallowing reflexes .................................. 22

Light‐reflex ........... ................. 23

Equilibrium, sight, smell and hearing ............ 27.5

Co‐ordinated action (walking, etc.) ..... ....... 28

2. A special vibrissae reflex is described. This occurs readily at 20°.

3. In the initiation and subsidence of stepping movements at low temperatures, a definite march or order is observed.

4. A regular alternation between shivering and inspiration occurs between 22° and 24°.

5. Exaggerated tonic spasms of the postural musculature occurs when the temperature of the recovering animal stands between 21° and 2°.

6. In its progressive effects gradual cooling shows a strong similarity to the induction of anaesthesia, consciousness becoming abolished gradually and disappearing between 27° and 25°, while the ordinary reflexes are still maintained (24° to 19°). At low temperatures (19° or 20°) the pupil becomes constricted, to dilate widely just before death.

7. No condition resembling “artificial hibernation” can be said to occur when a homoiothermic animal such as the cat is reduced to very low body temperatures; a definite thermogenic ability is retained even at 19°, from which temperature spontaneous recovery is effected in 10 to 12 hours.

8. The activities of the heart, respiratory muscles and abdominal viscera are probably wholly responsible for an initial small rise in body temperature, but spontaneous shivering and stepping movements and an exaggerated muscular tonicity occurring above 20° are the chief factors in heat production and hence in recovery of the animal.

9. So far as can be determined, death from exposure to cold is due to paralysis of the respiratory centre in the medulla oblongata.
NERVOUS CONNECTIONS OF THE MAMMALIAN SPLEEN, INCLUDING AN ACCOUNT OF CERTAIN VISCEROMOTOR AND OTHER ABDOMINAL REFLEXES
Authors: Cleland J. G. P. , Tait John
Published: December 2014

1. The splenic nerve of the dog contains at least two sets of efferent fibres, distinct in their anatomical arrangement and in the form of contraction they induce, the one set being probably arteriomotor, the other trabeculomotor.

2. Afferent fibres are present in all trunks of the splenic nerve.

3. Certain discrete segments of the splenic vein and of its main branches are endowed with special contractility. The segments in question form the terminal stations of particular nerve‐twigs from a main venomotor trunk, electrical stimulation of which thus causes local bands of contraction in the specially innervated regions.

4. The splenic venomotor fibres join the left phrenic nerve in the mid‐cervical region. Coursing with it as non‐medullated fibres, they eventually perforate the diaphragm, where for a time they accompany the inferior phrenic artery. Deviating towards the cceliac ganglion, they next join company with the splenic vein, and are eventually distributed to localised parts of the vein.

5. Physiological dilatation of the spleen is due to passage of nervous impulses down these venomotor fibres. This conclusion follows from the fact that on electrical stimulation of these fibres the resulting engorgement of the spleen corresponds in degree and in duration to the contraction of the splenic vein; from the further fact that when the venomotor fibres degenerate after section, the spleen remains in a state of partial contraction; and from the fact that section of these fibres abolishes reflex dilatation. The venomotor fibres thus form the efferent pathway for physiological dilatation.

6. The muscles of the ventral abdominal wall are maintained in a condition of steady postural tone, which, however, is momentarily inhibited at the commencement of each inspiration.

7. When any given abdominal muscle is suddenly stretched or squeezed, both it and the other abdominal muscles on the same side exhibit a strong reflex contraction. At the same time the tone of the abdominal muscles of the opposite side is by reciprocal action temporarily inhibited.

8. Increased tonic contraction, unaccompanied by inspiratory relaxation, occurs in particular regions of the ventral abdominal musculature as a result of effective stimulation of particular viscera through their afferent nerve fibres. The portion of this musculature innervated from the 9th thoracic segment upwards on the left side is particularly responsive to stimulation of the afferent nerve fibres of the splenic nerve. Under more powerful stimulation of the splenic afferents, the region involved in reflex contraction may extend from this special splenic area to a correspondingly delimited area on the opposite side. The above observations may well have a corresponding clinical application.

9. The afferent fibres for the splenic visceromotor reflex enter the spinal cord by the 5th, 6th, 7th, and 8th dorsal roots and are confined to the left side.
THE ACTION OF ADRENALINE AND OF CERTAIN DRUGS UPON THE ISOLATED CRUSTACEAN HEART
Authors: Bain W. A.
Published: December 2014

1. The action of adrenaline, ephedrine, ergotoxine, pilocarpine, and atropine has been studied on the heart of the crabs Maia squinado, Cancer pagurus, and Carcinus moenas.

2. A method for the perfusion of the isolated heart in these genera is described.

3. Adrenaline produces a marked acceleration of the rhythm and an increase in tone of the heart‐muscle in all cases.

4. In Cancer, in addition to the above effects, there is a pronounced increase in the amplitude of the beats.

5. The action of adrenaline is not reversible. In the lowest dilution in which it gives any effect, that effect is excitatory.

6. Ephedrine has no action on the crab heart.

7. Ergotoxine has a depressant action, but does not antagonise or reverse the action of adrenaline.

8. Pilocarpine produces an effect similar to that obtained with adrenaline.

9. Atropine has by itself no action on the heart in the dilutions employed, but antagonises the effect of pilocarpine.

10. Atropine has no effect on the response to adrenaline.

The author's acknowledgments are due to Dr E. J. ALLEN and Mr C. F. A. PANTIN for placing the facilities of the Marine Biological Laboratory at his disposal, and to Miss B. B. SMITH for assistance in conducting the experiments.
ON THE SUPPOSED PARTIAL LIBERATION OF HA; MOGLOBIN FROM THE MAMMALIAN ERYTHROCYTE
Authors: Saslow George
Published: December 2014

In the hæmolysis of mammalian red cells, whether by complement and amboceptor, freezing and thawing, saponin, or hypotonic saline, the amount of hæmoglobin liberated is determined by the number of cells hæmolysed. The cells give up no hæmoglobin until they hæmolyse, and then liberate all or very nearly all of it. There is no evidence that partial liberation of hæmoglobin occurs.
THE ACTION OF THE SKIN SECRETION OF THE SOUTH AFRICAN CLAWED TOAD
Authors: Gunn J. W. C.
Published: December 2014

The main active principle in the skin secretion of the South African clawed toad is a sympatho‐mimetic substance similar to but not identical with adrenaline.

In addition there is a varying proportion of a principle which stimulates the parasympathetic nerve‐endings.

The expenses of this research have been defrayed by the Council of the University of Cape Town.
A FLUID FOR MAMMALIAN SPERM‐SUSPENSIONS
Authors: Baker John R.
Published: December 2014

A buffered glucose‐saline fluid is described, designed to keep mammalian sperms at maximum activity for a maximum length of time at the temperature of the body. Sperms from the epididymis are suspended in this fluid in small uncorked test‐tubes in a damp chamber maintained at 37°C.
THE RATE OF RESPIRATION IN ERYTHROCYTES
Authors: Ramsey Robert , Warren Charles O.
Published: December 2014

1. Erythrocytes, both nucleated and non‐nucleated, have been found to respire at rates comparable to that of other resting tissues (30 to 70 mm. 3/ grm./ hr.).

2. The rate of oxygen consumption of erythrocytes in the intact animal is probably higher than the rates found in these experiments.

3. A great but temporary increase in the oxygen consumption of erythrocytes invariably occurs upon hæmolysis by lytic agents.

4. The increase in the oxygen consumption of erythrocytes upon hæmolysis is due to an increase in metabolism accompanying a liberation of cell contents.

5. The material which respires is not limited to particles of microscopic size alone, for the filtrate obtained by passing a hæmolysed red‐cell suspension through a Berkefeld filter still shows considerable respiratory activity.
THE EFFECT OF TEMPERATURE ON THE CARBOHYDRATE TOLERANCE IN XENOPUS LÆVIS (South African Clawed Toad)
Authors: Bosman Louis Pierre , Zwarenstein Harry
Published: December 2014

1. The normal blood‐sugar level in Xenopus lævis is about 44 mgs. per cent.

2. On injection of glucose solution, blood‐sugar curves are obtained which vary in rapidity of rise and return to normal, according to the temperature at which the experiments are conducted.

3. The renal threshold of Xenopus approximates that of man.

We desire to tender our thanks to the Research Grant Board of the Union of South Africa for financial assistance in this work, and also to Mr D. Duncan for his invaluable aid.
MODE OF ACTION OF RESPIRATORY STIMULANTS: II. MODE OF ACTION OF CARBON DIOXIDE
Authors: Selladurai S. , Wright Samson
Published: December 2014

1. In the cat (decerebrate or under chloralose anæsthesia) denervation of the carotid sinuses usually decreases the rate of breathing and the minute ventilation. The same result is obtained if the vagi are cut previously. It is concluded that the chemical composition of the blood stimulates the sinus nerve‐endings in the resting animal to discharge tonic excitor impulses to the respiratory centre.

2. The response to CO2 is usually reduced by denervation of the sinuses in the intact or vagotomised animal. It is concluded that the altered condition of the blood resulting from the raised CO2 concentration stimulates respiration in part reflexly from the carotid sinuses.

3. Vagotomy produces variable effects on the resting ventilation and on the response to C02. In animals under chloralose with sinuses denervated vagotomy frequently causes an enhanced reaction to C02. It is suggested that C02 may act differently on the various sensory components of the vagus nerve.

4. As a rule the response of the intact animal to CO2 is greater than that of the same animal with sinuses denervated and vagi divided.
ABSORPTION OF OXYGEN FROM THE PERITONEAL CAVITY AND THE STOMACH
Authors: Singh Inderjit
Published: December 2014

1. In the decapitated cat the lungs are about twenty times more efficient in absorbing oxygen than is the peritoneal cavity filled (500 c.c.) with pure oxygen; and about fifty times more efficient than the stomach containing 100 c.c. of oxygen. In a previous research the whole subcutaneous region gave results similar to the peritoneal cavity [Singh, 1932].

2. In human subjects living in Rangoon the pulse‐rate in the prone position is always higher than in the supine position. This is perhaps a climatic effect (Appendix I).

3. The cat's stomach when filled with 100 c.c. saline apparently slows the flow of fluid through the inferior vena cava when the animal is in the supine position (Appendix II).

I beg to thank Dr Argyll Campbell of the National Institute for Medical Research for help, advice and suggestions in the publication of these results.
THE EFFECT ON THE CELLS OF THE CAT'S SUBMAXILLARY GLAND OF THE AUGMENTED SECRETION
Authors: Rawlinson H. E.
Published: December 2014

The histological evidence supports the conclusion that there is a true augmented sympathetic secretion, and that it is due to an increased activity of the secretory cells, which normally act under the influence of the sympathetic nervous system.
STUDIES ON THE FILTRATION MECHANISM OF THE INTESTINAL LYMPH AND ON THE ACTION OF ACETYLCHOLINE ON IT AND ON THE CIRCULATION OF THE INTESTINAL VILLI
Authors: Königes Helmut Gordon , Ottó Mary
Published: December 2014

1. Measurements of blood‐pressure in the capillary, capillary veins, precapillary arteries of the intestinal villi of cats were carried out. The following values were found: blood‐pressure in the precapillary 37·3, in the capillary 31·3, in the postcapillary 24·3 mm. Hg.

2. At the same time the colloid osmotic pressure of the blood serum of the mesenterial artery and vein gave values of 19·4 and 26·8 mm. Hg. respectively.

3. The pressure in the central lymph‐vessel of the villus was also measured and found to be 24·5 mm. Hg.

4. The discussion of an individual case led to the conclusion that the hæmodynamical and osmotic pressure conditions in the villi are such as make filtration of the lymph possible.

5. The above values were estimated and recorded simultaneously before, during, and after the action of acetylcholine on the flow of lymph from the thoracic duct. The blood‐pressure in the carotid artery was also recorded. The observation of Beznák that acetylcholine causes an increase of blood‐pressure in the capillaries of the villi, which coincides with the fall of blood‐pressure in the medium‐sized arteries, is due to the relaxation of the precapillary arteries. Acetylcholine is regarded as a physiological lymph‐producer.

The authors are particularly indebted to Professor A. B. L. Beznák for his helpful advice and criticism.
THE EFFECT OF THE ALARM REACTION ON WATER EXCRETION
Authors: Karády St. , Browne J. S. L. , Selye H.
Published: December 2014

Experiments in the rat have confirmed the conception that an alarm reaction decreases the urine output irrespective of the stimulus which has been used to elicit it.

If during the course of an alarm reaction produced by any stimulus the same or any other stimulus is given, then the second stimulus not only fails to cause water retention but actually increases urine output.

These findings are in good accord with the assumption that two alarm reactions cannot be elicited in rapid succession, and that an alarm reaction produced by one stimulus raises the resistance of the organism both against this stimulus and against any other alarming agent.
THE EFFECT OF PONTINE TRANSECTION ON THE BLOOD‐SUGAR LEVEL OF THE DECEREBRATED FASTING CAT
Authors: Noltie H. R.
Published: December 2014

Mid‐brain decerebration in the fasting cat resulted, an hour later, in an average blood sugar of 220 mg. per cent., tending to rise to about 250 mg. in 3 hours' time, thereafter falling slowly. When decerebration was through the pons, the level was at first some 30 mg. higher, and in 4 hours rose to almost 340 mg.

The initial high sugar consequent on mid‐brain decerebration was not maintained in absence of the adrenals (removed just after decerebration).

“Bleeding back” behind the tentorium disturbed markedly both respiration and blood‐sugar concentration, preventing the usual fall of the latter.

Destruction of the pituitary, immediately after decerebration, did not make the rate of change of blood sugar any different from that in animals where it was left in situ (though cut off from the brain stem).

Cutting, at the start of the experiment, all the structures at the liver hilum, save the portal vein, did not alter the usual behaviour of the blood sugar of the decerebrate animal. Cutting at a later stage was followed by a slight rise in blood pressure, and an average rise of 50 mg. in blood sugar, apparent even in the adrenalectomised animal.

High concentrations of liver glycogen did occur 3 hours after decerebration but the average value was 1–3 per cent. Decerebrate animals with high liver glycogen at this stage usually had a high initial, slowly falling blood sugar.

Pontine transection some time after decerebration was followed by an average rise in blood sugar of 70 mg. A perceptible, though very small, rise in sugar occurred in absence of adrenals or of hepatic nerves (the latter were cut about 3 hours after decerebration). If the nerves had been out immediately after decerebration the rise in sugar following transection was just as great as when both adrenals and nerves were intact. In absence of adrenals and hepatic nerves, transection of the pons did not interrupt the trend of blood sugar evidenced prior to the section.

The main cause of the blood‐sugar rise following transection of the pons of the fasting decerebrate animal is certainly liberation of adrenaline from the suprarenals.

A considerable rise in blood pressure followed pontine transection even in the adrenalectomised decerebrate animal.

Destroying the hepatic nerves by tearing and application of phenol left an appreciably higher liver glycogen content than when all the hilum structures save the portal vein were cut, suggesting that the arterial flow to the liver may be of consequence in this connection.

The author acknowledges with thanks his indebtedness to the Medical Research Council for a grant in aid of expenses; to Professor Brocklehurst for facilities in the Department of Physiology, University of Bristol, where part of the investigation was carried out; to the late Professor J. J. R. Macleod, and to Professor A. Hemingway and Dr. J. M. Peterson for their interest and encouragement.
THE INFLUENCE OF SODIUM EVIPAN ON THE HEART AND CIRCULATION
Authors: Das S. C.
Published: December 2014

1. Intravenous injection of sodium evipan always causes a fall of blood‐pressure. This fall is not due to the reaction of the solution, but is partly due to vasodilation and partly to cardiac depression.

2. Perfusion of cat's leg in situ gives evidence of direct vasodilatation as well as of vasomotor depression.

3. Auricle strip of frog shows 10 per cent. depression with 1 in 50,000 of evipan, 25 per cent. with 1 in 20,000, 40 per cent. with 1 in 10,000, 60 per cent. with 1 in 5000, and 95 to 100 per cent. with 1 in 2000 concentration.

4. Myocardiographic record of cat's heart in situ indicates auricular and ventricular depression even with small doses of evipan, showing that the cardiac factor plays a definite part in causing a fall of blood‐pressure.

5. This depressant effect on circulatory system can be minimised to a great extent by giving the dose in fractions at short intervals, and still better by continuous intravenous infusion.

The author gratefully acknowledges his indebtedness to Professor A. J. Clark for his advice and help throughout the course of his work.
THE EFFECT OF ASCORBIC ACID (VITAMIN C), CALCIUM ASCORBATE, AND CALCIUM GLUCONATE ON THE REGENERATION OF BONE IN RATS
Authors: Bourne Geoffrey , MacKinnon MacKenzie
Published: December 2014

A new technique has been described for the estimation of the power of a substance to accelerate the healing of bone.

It has been found by this method that neither vitamin C nor calcium glucono‐galacto‐gluconate in the doses given accelerates the healing of bone in rats on an adequate diet when injected subcutaneously.

On the other hand, it has been found that calcium ascorbate injected subcutaneously into rats does statistically increase the amount of bone regenerated by the end of 7 days.

The vitamin C used for these experiments was Redoxon, Roche, and I am greatly indebted to Roche Products Ltd., not only for the vitamin C, but also for making the calcium ascorbate specially for this work at my request.
FURTHER OBSERVATIONS ON THE INTERMEDIATE LOBE PITUITARY HORMONE
Authors: Landgrebe F. W. , Reid E. , Waring H.
Published: December 2014

1. Modifications of the Landgrebe‐Waring [1941] method for obtaining a high yield of potent melanophore expanding hormone (“B”) are described.

2. The best product L. R. W.1 contains per mg.—

85,000 L. W. units “B” 1 Int. Unit pressor.

3. Properties of our new extracts are compared with those of Stehle's [1936] extract.

4. Extracts may be rich in “B” and yet exert no hyperglycæmic or anti‐insulin effects.

5. The hyperglycæmia evoked by 0·1 mg. adrenaline is largely inhibited by subcutaneous injection of 0·25 mg. L. R. W.1. It is not claimed that this inhibition is due to “B” hormone itself.

6. No significant amounts of “B” were detected in the blood or urine of untreated rabbits.

7. Aqueous extracts of normal rabbit liver contain a melanophore excitant that, with the tests at present available, is indistinguishable from pituitary “B”‐hormone.
SERUM CHOLINE ESTERASE IN BARBITURATE ADDICTION AND EPILEPSY
Authors: Schütz F.
Published: December 2014

1. The previously described decrease of serum choline esterase after prolonged administration of barbiturates in man was studied in epileptics after sudden withdrawal of the drug. The number of seizures then rises sharply to a maximum, while the choline esterase is still at a low level.

2. The seizures become less frequent again when the choline esterase starts to rise, and usually disappear completely when the choline esterase has just reached what proves to be, in the particular individual, its highest level.

3. When the drug is given, the choline esterase decreases to a minimum in about three weeks, whereas the number of seizures is minimal in a few days.

4. A time sequence of the abstinence symptoms was noted, the withdrawal psychosis appearing first and wearing off when the grand mals were at their peak, whereas the latter preceded the maximal frequency of petit mal seizures.

5. In an unselected group of cryptogenic (idiopathic) epileptics, when under no treatment for some time, a slightly higher average value of serum choline esterase was found than the normal average, the difference being statistically not significant. In some of the epileptics, however, much higher values were found than were ever found in normals. The possible existence of one group of epileptics, characterised by a high choline esterase, is discussed.

6. After the withdrawal of the drug the narcotic effect seems to wear off more rapidly than the choline esterase increases. Thus the cholinergic system, free from narcotic and probably at a high level of activity, is left with an inadequate amount of choline esterase. This discrepancy probably accounts for the abstinence symptoms.

7. Because of the relative lack of choline esterase during the period of abstinence symptoms, excessive cholinergic activity is assumed to exist. A number of indications for this are found, and its possible rôle in the production of seizures is discussed. Some diverse features, such as the peak incidence of seizures during the night, the precipitating action of alcohol in epilepsy, and some features in the electro‐encephalograms, become more understandable from this viewpoint.

I am greatly indebted to Professor P. C. Cloake for his interest and helpful encouragement in this investigation. I am also very grateful to Dr. J. J. O'Reilly, Medical Superintendent of the Birrningham City Mental Hospital, Winson Green, for providing me with the necessary material from the patients under his care, for altering within limits of safety the treatment given to a number of them as this appeared important for these experiments, and for his kind help. I am also grateful to G. Hoyle and D. Marshall for valuable technical assistance.
ON THE METABOLISM OF HISTAMINE
Authors: Alexander Frank
Published: December 2014

The skin of the mice was found to contain more than 60 per cent. of all the histamine in the body.

A large dose of histamine was cleared partly by excretion and partly by some other mechanism. Excretion occurred through the kidney, and only whilst a high concentration was present in the body. The whole of a large dose was removed within twenty‐four hours of administration.
Acetylcholine‐evoked currents in cultured neurones dissociated from rat parasympathetic cardiac ganglia.
Authors: Fieber L A , Adams D J
Published: December 2014

1. The properties of acetylcholine (ACh)‐activated ion channels of parasympathetic neurones from neonatal rat cardiac ganglia grown in tissue culture were examined using patch clamp recording techniques. Membrane currents evoked by ACh were mimicked by nicotine, attenuated by neuronal bungarotoxin, and unaffected by atropine, suggesting that the ACh‐induced currents are mediated by nicotinic receptor activation. 2. The current‐voltage (I‐V) relationship for whole‐cell ACh‐evoked currents exhibited strong inward rectification and a reversal (zero current) potential of ‐3 mV (NaCl outside, CsCl inside). The rectification was not alleviated by changing the main permeant cation or by removal of divalent cations from the intracellular or extracellular solutions. Unitary ACh‐activated currents exhibited a linear I‐V relationship with slope conductances of 32 pS in cell‐attached membrane patches and 38 pS in excised membrane patches with symmetrical CsCl solutions. 3. Acetylcholine‐induced currents were reversibly inhibited in a dose‐dependent manner by the ganglionic antagonists, mecamylamine (Kd = 37 nM) and hexamethonium (IC50 approximately 1 microM), as well as by the neuromuscular relaxant, d‐tubocurarine (Kd = 3 microM). Inhibition of ACh‐evoked currents by hexamethonium could not be described by a simple blocking model for drug‐receptor interaction. 4. The amplitude of the ionic current through the open channel was dependent on the extracellular Na+ concentration. The direction of the shift in reversal potential upon replacement of NaCl by mannitol indicates that the neuronal nicotinic receptor channel is cation selective and the magnitude suggests a high cation to anion permeability ratio. The cation permeability (PX/PNa) followed the ionic selectivity sequence Cs+ (1.06) greater than Na+ (1.0) greater than Ca2+ (0.93). Anion substitution experiments showed a relative anion permeability, PCl/PNa less than or equal to 0.05. 5. The nicotinic ACh‐activated channels described mediate the responses of postganglionic parasympathetic neurones of the mammalian heart to vagal stimulation.
Effect of opioid peptides on circular muscle of canine duodenum.
Authors: Bauer A J , Szurszewski J H
Published: December 2014

1. The effects of opioid peptides on inhibitory transmission in the circular muscle layer of canine duodenum were investigated in vitro using simultaneous mechanical and intracellular electrical recording techniques. 2. Exogenously added [Met5]enkephalin, [Leu5]enkephalin and dynorphin (1‐13) decreased the amplitude of non‐adrenergic, non‐cholinergic inhibitory junction potentials (IJPs) evoked by transmural nerve stimulation. 3. A selective delta‐receptor agonist, DPDPE ([D‐Pen2, D‐Pen5]enkephalin), and a selective mu‐receptor agonist, PL017 (Try‐Pro‐NMePhe‐D‐Pro‐NH2), decreased the amplitude of IJPs whereas a selective kappa‐receptor agonist, U‐50,488H ([trans‐3,4‐dichloro‐N‐methyl‐N‐(2‐91‐pyrolidinyl)‐cyclohexyl]‐ benzeneacetamide methanesulphonate), in large doses (1 microM) produced only a small reduction. 4. A selective delta‐receptor antagonist, ICI‐174,864, blocked the effect of DPDPE but not that of PL017 suggesting the presence of distinct delta‐ and mu‐opioid receptors on inhibitory motor nerves. 5. Exogenously added dynorphin (1‐13) decreased the amplitude of IJPs. delta‐Opioid receptors appeared to be involved because ICI‐174,864, a selective delta‐antagonist, blocked the inhibitory effect of exogenously added dynorphin (1‐13). 6. The inhibitory effect of the opioid peptides was still observed in preparations of circular muscle devoid of myenteric and submucosal plexuses, indicating that the site of action was on inhibitory motor nerve fibres located within the circular muscle layer and not on neuronal cell bodies in the enteric plexuses. 7. It was concluded that in the canine small intestine, opioid peptides could modulate release of inhibitory transmitter(s) at or near nerve terminals of inhibitory motor nerves innervating circular muscle cells.
Signalling of a step‐like intensity change of noxious mechanical stimuli by dorsal horn neurones in the rat spinal cord.
Authors: Laird J M , Cervero F
Published: December 2014

1. Single‐unit extracellular recordings were made from thirty‐one dorsal horn neurones in the sacral spinal cord of barbiturate‐anaesthetized rats. Each neurone was tested with four noxious mechanical pinches applied to its receptive field on the tail. Each pinch lasted 120 s, with a step‐like change in intensity after 60 s. In two pinches the step increased the intensity, from 4 to 6 N or from 6 to 8 N, and in two the step decreased the intensity, from 8 to 6 N or from 6 to 4 N. 2. The ability of the neurones to signal these step changes in intensity was examined. Five neurones with an exclusively low‐threshold afferent input (class 1) were tested, and found to fire only briefly at the start of the 120 s stimulus. Neurones with a high‐threshold input (nociceptive neurones), either exclusively (class 3; n = 10) or in addition to a low‐threshold input (class 2: n = 16), responded throughout the 120 s stimuli. 3. Nociceptive dorsal horn neurones have been divided into two groups of ‘good’ and ‘poor’ encoders on the basis of their response to the step changes in intensity. 4. ‘Good’ encoders (n = 13) were neurones signalling both a step increase and a step decrease in intensity, of which seven were class 2 and six class 3, five recorded in the superficial dorsal horn and eight in the deep dorsal horn. 5. ‘Poor’ encoders (n = 13) were neurones which failed to signal one or both of the step changes in intensity, of which nine were class 2 and four class 3, three recorded in the superficial dorsal horn and ten in the deep dorsal horn. 6. These results demonstrate that neurones with similar input properties and location are not necessarily a homogeneous group in terms of their processing of nociceptive stimuli. Moreover, they suggest that subgroups of both class 2 and class 3 and of superficial and deep dorsal horn neurones contribute to the different components of a nociceptive response. 7. We propose that the output and projection target of a particular dorsal horn neurone are more important than its afferent input in determining its role in nociceptive processing.
Noradrenaline‐evoked cation conductance recorded with the nystatin whole‐cell method in rabbit portal vein cells.
Authors: Wang Q , Large W A
Published: December 2014

1. Noradrenaline‐evoked currents were studied with the perforated patch technique (nystatin in the patch pipette) in freshly dispersed rabbit portal vein cells. 2. With potassium‐containing solutions noradrenaline produced an inward current at ‐50 mV and an outward current (IK(Ca] at 0 mV. In potassium‐free conditions noradrenaline elicited two distinct membrane currents which could be differentiated according to their sensitivity to the presence of caffeine in the bathing solution. One current was blocked whereas the second response was unaffected by caffeine. 3. The reversal potential (Er = ‐2.0 mV) of the caffeine‐sensitive current was altered when external chloride was replaced with more permeant anions but Er was not changed when external sodium was replaced by Tris. Therefore the caffeine‐sensitive current appears to be a calcium‐activated chloride current (ICl(Ca]. 4. Er (+6.0 mV) of the caffeine‐insensitive current was not altered by anion substitution but was changed when external sodium was replaced by Tris and barium ions. Thus the caffeine‐insensitive conductance is a non‐selective cation current (Icat). 5. When external NaCl was replaced by BaCl2, Er was shifted to more positive potentials which suggests that the cation conductance is more permeable to barium than to sodium. Icat was not affected by 10(‐6) M‐nifedipine. 6. The steady‐state current‐voltage relationship was linear between ‐50 and +50 mV for ICl(Ca) but the cation conductance mechanism displayed pronounced inward rectification and little outward current flowed across the membrane at positive potentials. 7. Caffeine (which releases calcium from internal stores) and the calcium ionophore ionomycin, which are expected to increase intracellular calcium concentration, evoked ICl(Ca) but not Icat. Thus ICl(Ca) but not Icat can be activated directly by an increase in intracellular calcium concentration. 8. When calcium was removed from the bathing solution the amplitude of Icat was not altered at early times in Ca(2+)‐free conditions but was abolished after 10 min. Icat was readily activated by noradrenaline in the presence of ionomycin, which inactivated ICl(Ca). A permissive role for calcium in the generation of Icat is suggested. 9. The times between the application of noradrenaline and the onset of the chloride and cationic conductances were similar (0.75 and 0.9 s respectively). In contrast the rise time (3.9 s) and half‐decay time (11 s) of Icat were much longer than the corresponding values of ICl(Ca) (respectively 1.9 and 2 s). In high‐barium solution noradrenaline sometimes evoked a response that lasted for up to 10 min.(ABSTRACT TRUNCATED AT 400 WORDS)
Receptor‐activated calcium influx in human airway smooth muscle cells.
Authors: Murray R K , Kotlikoff M I
Published: December 2014

1. Fluorescence measurements of intracellular calcium concentrations ([Ca2+]i) were made on cultured human airway smooth muscle cells using the dye Fura‐2. The response to either histamine (100 microM) or bradykinin (1 microM) was biphasic, with a transient increase in [Ca2+]i followed by a sustained [Ca2+]i increase lasting many minutes. The average steady‐state (plateau) [Ca2+]i following agonist activation was 267 +/‐ 5 nM, whereas the average basal [Ca2+]i was 148 +/‐ 4 nM. 2. The sustained rise in [Ca2+]i required the continued presence of either histamine or bradykinin and was dependent on extracellular Ca2+. The magnitude of the transient rise in [Ca2+]i was not dependent on extracellular Ca2+. Sustained, receptor‐activated rises in [Ca2+]i were rapidly abolished by chelation of extracellular Ca2+, or addition of non‐permeant polyvalent cations, whereas these agents had minor effects in the absence of agonist. These data indicate that the sustained increase in [Ca2+]i was dependent on receptor‐activated Ca2+ influx. 3. Receptor‐activated Ca2+ influx was not affected by treatment with organic Ca2+ channel antagonists (nifedipine (10 microM), nisoldipine (10 microM) or diltiazem (10 microM] or agonists (Bay K 8644 (500 nM to 10 microM) or Bay R 5417 (500 nM]. The magnitude of the sustained rise was also not affected by pre‐treatment with ouabain (100 microM) indicating little involvement of Na(+)‐Ca2+ exchange in the influx mechanism. 4. Receptor‐activated Ca2+ influx could be completely inhibited by several polyvalent cations (Co2+, Mn2+, Ni2+, ‐Cd2+ or La3+). Quantitative estimates of the potency of block were obtained for Ni2+ and La3+. These measurements indicate that the pKi for Ni2+ was 3.6 and for La3+ was 3.5. 5. Both Mn2+ and Co2+ ions caused a time‐dependent quench of intracellular Fura‐2; however, permeation of neither ion was increased following receptor activation, indicating that the influx pathway is not permeable to these cations. 6. Fura‐2 was used to monitor the rate of Ba2+ entry into airway smooth muscle cells by monitoring the Ca(2+)‐Fura‐2 and Ba(2+)‐Fura‐2 isosbestic points as well as the 340 and 380 nm signals. Cell activation did not increase the rate of Ba2+ entry indicating that the Ca2+ influx pathway was poorly permeant to Ba2+ ions. Ba2+ (2 mM) was able to inhibit Ca2+ entry as shown by its effects on the Ba(2+)‐independent, Ca(2+)‐dependent wavelength (371 nm). 7. The voltage dependence of Ca2+ influx was examined before and after agonist‐induced activation. The effect of KCl‐induced depolarization prior to cell activation was to cause a slight increase in [Ca2+]i.(ABSTRACT TRUNCATED AT 400 WORDS)
Glucose stimulation of ouabain‐resistant efflux of Na+ from rat pancreatic islets.
Authors: Ali L , Hellman B
Published: December 2014

1. Integrating flame photometry was employed for measuring the mobilization of sodium from rat pancreatic islets after substitution of extracellular Na+ by N‐methylglucamine. 2. Glucose accelerated the initial loss of sodium both in the absence and presence of ouabain (1 mM). In the latter case the effect was maximal at 5 mM of the sugar. 3. Amiloride (0.1 mM), an inhibitor of Na(+)‐H+ exchange, prevented the effect of glucose on the ouabain‐resistant Na+ efflux, increasing the rate of outward transport in the absence of the sugar. 4. Extracellular K+ and arginine (10 mM) mimicked the action of glucose in promoting a ouabain‐resistant mobilization of sodium. 5. Whereas the hypoglycaemic sulphonylurea tolbutamide (100 microM) did not modify the outward transport of Na+, the ouabain‐resistant component of this process was partially suppressed after bumetanide (100 microM) inhibition of the chloride‐dependent co‐transport of Na+ and K+. 6. It is suggested that the glucose‐induced lowering of the steady‐state content of islet sodium involves an increased outward transport mediated at least in part by mechanisms other than stimulation of the Na(+)‐K+ pump.
Na(+)‐activated K+ channels and voltage‐evoked ionic currents in brain stem and parasympathetic neurones of the chick.
Authors: Dryer S E
Published: December 2014

1. Patch‐clamp and computer‐modelling techniques were used to study the activation of Na(+)‐activated K+ channels (IK(Na] in dissociated neurones from the embryonic chick ciliary ganglion and the embryonic chick brain stem. 2. Numerical solutions of diffusion equations suggested that Na+ accumulation as a result of Na+ influx through voltage‐sensitive Na+ channels (INa) is insufficient to allow for alteration in the gating of IK(Na) channels. 3. Whole‐cell recordings using two independent micropipettes were made from chick ciliary‐ganglion neurones. These showed that transient outward currents were present only when there were clear indications of incomplete voltage clamp. 4. Single‐electrode whole‐cell recordings from ciliary‐ganglion neurones showed that transient tetrodotoxin (TTX)‐sensitive outward currents were present, but only when partial TTX blockade produced significant alterations in the kinetics of INa. In cells that were properly voltage clamped, there was no effect of TTX on the kinetics of INa or on voltage‐evoked outward currents. 5. Examination of the relationship between peak INa and the command potential showed that transient outward currents were only present in neurones that showed sharp deviations from the behaviour expected of a cell that is adequately voltage clamped. Transient outward currents were not present in cells that were adequately voltage clamped. 6. Application of TTX to isolated outside‐out patches obtained from ciliary ganglion neurones eliminated voltage‐evoked inward currents but had no effect on outward currents. 7. Isolated inside‐out patches obtained from ciliary‐ganglion neurones did not contain IK(Na) channels. These patches usually contained Ca(2+)‐activated K+ channels (IK(Ca] with a unitary conductance of around 200 pS when [K+]o = 150 mM and [K+]i = 75 mM. 8. Two‐electrode whole‐cell recordings from cultured brain stem neurones showed that transient outward currents were present only when there were clear indications of incomplete voltage clamp. 9. Application of TTX caused blockade of inward but not outward currents in brain stem neurones voltage clamped with a single whole‐cell pipette. TTX had no effect on the kinetics of INa. Application of TTX to outside‐out patches isolated from the same cells blocked only the inward currents. 10. Isolated inside‐out patches obtained from brain stem neurones contained IK(Na) channels that could be activated by exposure of the cytoplasmic face of the patch membrane to 75 mM‐Na+. These channels had a predominant conductance state of around 100 pS when [K+]o = 150 mM and [K+]i = 75 mM. The IK(Na) channels were not activated by 1 mM‐Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)
Characteristics of fluid secretion from isolated rat pancreatic ducts stimulated with secretin and bombesin.
Authors: Ashton N , Argent B E , Green R
Published: December 2014

1. Micropuncture techniques were used to study the cellular mechanisms of fluid secretion by interlobular ducts isolated from the pancreas of copper‐deficient rats. 2. Perifusing ducts with a calcium‐free buffer containing 5 mM‐EGTA reduced the volume of fluid secreted in the presence of 10 nM‐bombesin by 62%, whereas fluid secretion measured in the presence of 10 nM‐secretin was reduced by only 26%. 3. The anion selectivities of the fluid secretions evoked by secretin and bombesin were different. The anion sequence for secretin was: Br‐ = I‐ = NO3‐ = Cl‐ (1.0) much greater than thiocyanate = gluconate (0.3); whereas the sequence for bombesin was: Br‐ = Cl‐ (1.0) greater than I‐ = NO3‐ (0.6) greater than thiocyanate = gluconate (approximately 0.3). 4. SITS (4‐acetamido‐4'‐isothiocyanatostilbene‐2,2'‐disulphonic acid; mM), reduced fluid secretion measured in the presence of bombesin by 61%, but had no effect on the response to secretin. 5. The K+ channel blockers, barium (3 mM) and tetraethylammonium (TEA; 10 mM), inhibited fluid secretion measured in the presence of both secretin and bombesin by between 52 and 66%. 6. From these results, we conclude that secretin and bombesin may utilize different intracellular signalling pathways and, furthermore, may activate different anion secretory mechanisms within the pancreatic ductal epithelium. However, the effect of the potassium channel blockers is consistent with both peptides activating secretory mechanisms which are electrogenic, and which depend for their operation on potassium efflux across the basolateral membrane of the duct cell.
Intracellular pH and its regulation in isolated type I carotid body cells of the neonatal rat.
Authors: Buckler K J , Vaughan‐Jones R D , Peers C , Nye P C
Published: December 2014

1. The dual‐emission pH‐sensitive fluoroprobe carboxy‐SNARF‐1 (carboxy‐seminaptharhodofluor) was used to measure pHi in type I cells enzymically dispersed from the neonatal rat carotid body. 2. Steady‐state pHi in cells bathed in a HEPES‐buffered Tyrode solution (pH 7.4) was found to be remarkably alkaline (pHi = 7.77) whereas cells bathed in a CO2‐HCO3(‐)‐buffered Tyrode solution (pH 7.4) had a more ‘normal’ pHi (pHi = 7.28). These observations were further substantiated by using an independent nullpoint test method to determine pHi. 3. Intracellular intrinsic buffering (beta, determined by acidifying the cell using an NH4Cl pre‐pulse) was in the range 7‐20 mM per pH unit and appeared to be dependent upon pHi with beta increasing as pHi decreased. 4. In cells bathed in a HEPES‐buffered Tyrode solution, pHi recovery from an induced intracellular acid load (10 mM‐NH4Cl pre‐pulse) was inhibited by the Na(+)‐H+ exchange inhibitor ethyl isopropyl amiloride (EIPA; 150 microM) or substitution of Nao+ with N‐methyl‐D‐glucamine (NMG). Both EIPA and Nao+ removal also caused a rapid intracellular acidification, which in the case of Nao+ removal, was readily reversible. The rate of this acidification was similar for both Nao+ removal and EIPA addition. 5. Transferring cells from a HEPES‐buffered Tyrode solution to one buffered with 5% CO2‐HCO3‐ resulted in an intracellular acidification which was partially, or wholly, sustained. The rate of acidification upon transfer to CO2‐HCO3‐ was considerably slowed by the membrane permeant carbonic anhydrase inhibitor, acetazolamide, thus indicating the presence of the enzyme in these cells. 6. In CO2‐HCO3(‐)‐buffered Tyrode solution, pHi recovery from an intracellular acidosis (NH4+ pre‐pulse) was only partially inhibited by EIPA or amiloride whereas Nao+ removal completely inhibited the recovery. The stilbene DIDS (4,4‐diisothiocyanatostilbenedisulphonic acid, 200 microM) also partially inhibited pHi recovery following an induced intracellular acidosis. Furthermore, the pre‐treatment with 200 microM‐DIDS of a pre‐acidified cell in Na(+)‐free Tyrode solution completely inhibited pHi recovery when Nao+ was reintroduced together with concomitant addition of 150 microM‐EIPA. We conclude, that in the presence of CO2‐HCO3‐, a Na(+)‐ and HCO3‐dependent (DIDS inhibitable) mechanism aids acid extrusion.(ABSTRACT TRUNCATED AT 400 WORDS)