bluuebunny/crossref_metadata_2025 huggingface dataset:
The transcapillary exchange of thyroid hormones and thyroxine‐binding proteins between blood and tissue fluids.
Authors: Simpson-Morgan M W , Sutherland R L
Published: December 2014

A study has been made of the relative importance of potien bound and unbound hormone in the exchange of thyroid hormones between blood and interstitial fluid. 2. When [I] tyroxine (or thriiodothyronine) and [I] human serum albumin were injected simultaneously into the circulation of sheep with chronic lymphatic fistulae, the thyroid hormones were removed from the circulation and apperaed in all lymph samples at a greater fractional rate than human serum albumin. 3. The steady‐state lymph/plasma concentrations ratios of the two specific thyroxine binding proteins were similar to each other and to those of albmin and total thyroxine. 4. Gel filtration studies indicated that the two specific thyroxine binding proteins, ovine serum albumin and human serum albumin, were all of similar molecular size. 5. Concentrations of unbound thyroxine in plasma and various samples of lymph from the one animal were similar. 6. Increasing the proportion of thyroid hormone that was unbound resulted in an increase rate of equilibration of labelled hormone between blood plasma and lymph. 7. Perfusion of the popliteal lymph node demonstrated that thyroid hormones were removed from lymph during its passage through the node. The amount removed was related to the proportion of hormone in the unbound state.
Kinetics of active sodium transport in rat proximal tubules and its variation by cardiac glycosides at zero net volume and ion fluxes. Evidence for a multisite sodium transport system.
Authors: Györy A Z , Lingard J M
Published: December 2014

1. Transepithelial Na concentration difference, deltaCNa, across proximal tubules of rat kidney was measured at varying intraluminal Na concentrations (CNainfinity) under conditions of zero net volume and Na flux. Simultaneous stopped‐flow intratubular and artificial peritubular capillary perfusion techniques were used together with intratubular raffinose to achieve zero net fluxes. Under these conditions in rat proximal tubules, deltaCNa represents active transport, JactNa, factored by permeability, PNa, plus an electrical factor depending on transepithelial potential difference. 2. The relationship between CNainfinity and deltaCNa appeared sigmoidal with saturation being reached when intratubular Na was above 80 m‐mole/kg. In the presence of ouabain (10(‐2)M) and scilliroside (10(‐3)M) the relationship remained the same. The maximum deltaCNa was reduced by approximately 50% by cardiac glycoside inhibition whereas the half‐saturation constant was essentially unchanged. These changes from the control represent simple non‐competitive inhibition by the cardiac glycosides. 3. Absence of potential difference (p.d.) measurements precludes exact description of the relation between true active transport and substrate concentration but much evidence indicates that the apparently sigmoid relation in the presence and absence of cardiac glycoside inhibition, would be retained if correction of deltaCNa values were possible. Such results could then be explained if there are at least three or more sites for Na on the pump system, of which at least two are not cardiac glycoside sensitive. They would also unequivocally exclude the presence of a single‐site single‐pump system or the simple algebraic addition of two such units since the kinetic curves for both would be hyperbolic rather than sigmoidal.
A study of the nycthemeral cycle of behavioural temperature regulation in man.
Authors: Cabanac M , Hildebrandt G , Massonnet B , Strempel H
Published: December 2014

1. Four human subjects were rendered hyperthermic and hypothermic by immersion in warm and cool water, at 02.00, 08.00, 14.00 and 20.00 hr. Bath and oesophageal temperatures and pulse rate were recorded. Temperature preference was determined by operant behaviour and vote. The core temperature set‐point for behavioural thermoregulation was estimated from the behavioural results. 2. The results are in accord with those of previous studies of the nyethemeral cycling of autonomic responsiveness to heat and cold with a heating up phase before noon and a cooling down phase during the early night. 3. Subjective sensations and behavioural responses were also found to follow a nycthemeral cycle with a minimum before noon and a maximum at 20.00 hr. 4. The core temperature set point was 0‐7 degrees C higher after noon than before noon with a small phase advance from resting core temperature. This result suggests that the nycthemeral cyclic change in body temperature is due to a nycthemeral cyclic change in the set‐point near to which body temperature is kept by both autonomic and behavioural thermoregulatory responses.
Electrical properties of the rod syncytium in the retina of the turtle.
Authors: Schwartz E A
Published: December 2014

1. Intracellular responses were recorded from rods in isolated eye‐cups of the snapping turtle. Chelydra serpentina. Responses to flashes of small (less than 100 mum diameter) and large (1000 mum diameter) spots of 500 nm light were studied. 2. Responses produced by small and large diameter spots which delivered less than 0‐3 photons mum‐2 had the same shape. The responses produced by large spots were, however, nearly ten times greater in amplitude. The difference in amplitude is termed enhancement. 3. Perfusing an eye‐cup with a Co2+‐containing medium blocked synaptic transmission from receptors to horizontal cells but did not affect the responses of rods. 4. The membrane conductance of a single rod, estimated by three independent methods, was approximately 1‐2 X 10(‐9) MHo. 5. Enhancement can be predicted by a mathematical model which treats rods as an electrical syncytium. The space coefficient describing the spread of current is approximately 65 mum indicating that the coupling conductance between rods was relatively high. 6. When the intensity of a small spot was increased from 0‐3 photons mum‐2 up to 6 photons mum‐2, the shape of the response was unchanged. When the intensity of a large spot was increased to more than 0‐3 photons mum‐2, the voltage during the recovery phase was decreased. This decrease is termed disenhancement. 7. The voltages produced by bright, large and small diameter spots which delivered the same quantity of light to the impaled rod were compared. The voltage produced by a large diameter spot became for a short period during the recovery phase less than the voltage produced by a small diameter spot. This observation indicates that the response to a large spot included during recovery an active process which is not apparent in the response to a small spot.
A study of the vascular and acid‐secretory responses of the rat gastric mucosa to histamine.
Authors: Main I H , Whittle B J
Published: December 2014

1. The effects of histamine on gastric mucosal blood flow in the presence and absence of gastric acid secretion were studied in the rat. 2. Histamine, in doses greater than those required to stimulate maximal acid secretion, caused a small increase in mucosal blood flow per unit acid output. 3. When acid secretion was inhibited by methyl analogues of prostaglandin E2, histamine reduced arterial blood pressure and gave a dose dependent rise in mucosal blood flow. 4. When acid secretion was inhibited by the histamine H2‐receptor antagonists, burimamide and metiamide, histamine still increased mucosal blood flow. 5. The use of H1‐receptor antagonists to inhibit the histamine‐induced hyperaemia was made difficult by their vasodilator actions. 6. The selective histamine H2‐receptor agonist, 4‐methyl histamine, had no effect on arterial blood pressure in doses which stimulated acid secretion. The increase in mucosal blood flow which accompanied the stimulation of acid secretion was inhibited by the anti‐secretory prostaglandins and H2‐receptor antagonists. 7. The selective histamine H1‐receptor agonist, 2‐pyridyl ethylamine, had no effect on acid output but increased resting mucosal blood flow. 8. These results suggest that histamine H2‐receptors, primarily concerned with acid secretion, and H1‐receptors concerned with vasodilatation are both present in the rat gastric mucosa.
Subcellular localization of the heparin‐neutralizing factor in blood platelets.
Authors: Da Prada M , Jakábová M , Lüscher E F , Pletscher A , Richards J G
Published: December 2014

1. The distribution of the heparin‐neutralizing factor (platelet factor 4, PF4) in subcellular organelles of blood platelets of rabbits and man was investigated. 2. In both species the organelles storing 5‐hydroxytryptamine (5‐HT storage organelles) contained only trivial amounts of PF4. 3. In contrast, the content of PF4 was highest in the subcellular fractions rich in alpha‐granules. 4. In conclusion, PF4 is probably localized in the alpha‐granules and therefore the platelets contain at least two types of organelles (5‐HT organelles and alpha‐granules) capable of releasing their contents in response to the same stimuli, such as exposure to collagen, thrombin, etc.
Mode of stimulation by adenosine 3':5'‐cyclic monophosphate of the sodium efflux in barnacle muscle fibres.
Authors: Bittar E E , Chambers G , Schultz R
Published: December 2014

1. Giant fibres of the barnacle Balanus nubilus have been used as a preparation for studying the mode of action of cAMP on sodium transport. 2. It is shown that a concentration of cAMP as low as 10(‐6)M, when micro‐injected, causes a sharp rise in the radio‐Na efflux. Ouabain fails to reverse the cAMP effect. 3. The magnitude of the response of the Na efflux to cAMP is markedly reduced by pre‐injecting 100 or 500 mM‐EGTA solutions or by omitting Ca2+ from the bathing medium. Both together fail to bring about a greater reduction in the response. 4. The response to cAMP is greatly reduced by pre‐injecting the protein inhibitor of Walsh and practically abolished by pre‐injecting 500 mM‐EGTA and soaking in Ca‐free artificial sea water, ASW. 5. The Ca2+‐independent component of the Na efflux which is also stimulated by cAMP is shown to involve Na for H exchange. The magnitude of this exchange is governed by external pH. 6. The Na efflux into Ca2+‐free, Li+‐ASW is shown to be markedly stimulated by injecting cAMP, an effect which is enhanced by reducing external pH. 7. The Na efflux at 0 degrees C is stimulated by injecting cAMP. This is shown to be related to activation of the protein kinase by cAMP and to depend on the presence of external Ca2+. 8 (i) Ethacrynic acid when injected reduces the ouabain‐insensitive Na efflux into HEPES‐Ca2+‐free ASW at pH 6‐3. These same fibres show a marked response to cAMP. (II) The ouabain‐insensitive Na efflux into HCO3‐, Ca2+‐free ASW from fibres pre‐treated with ethacrynic acid fails to respond to external acidification. This is interpreted as indicating that ethacrynic acid inactivates the CO2‐sensitive adenyl cyclase system. These same fibres when injected with cAMP show a marked response. (iii) Stimulation of the ouabain‐insensitive Na efflux into HCO‐3, Ca2+‐free ASW by external acidification is reversed by injecting ethacrynic acid. These fibres when injected with cAMP show a reduced response. 9. It is concluded that: (i) stimulation of the Na efflux by injected cAMP is mainly due to activation of cAMP‐dependent protein kinase; (ii) the underlying exchange mechanism consists of Na:Ca and Na:H exchange. Interaction of Ca2+ with a phosphorylated membrane, thereby modifying permeability remains as a real possibility; (iii) the site of action of CO2 and ethacrynic acid is the adenyl cyclase system. 10. The implications of activation of the adenyl cyclase system by CO2 and Na:H exchange are briefly touched upon.
Antagonism by antipyretics of the hyperthermic effect of a prostaglandin precursor, sodium arachidonate, in the cat.
Authors: Clark W G , Cumby H R
Published: December 2014

1. Injection of sodium arachidonate (100‐400 mug) into lateral cerebral ventricles of unanaesthetized cats caused shivering and rapid development of dose‐related hyperthermic responses. Unless arachidonate is hyperthermogenic per se, this indicates that in vivo formation of prostaglandins, or perhaps an endoperoxide intermediate, can cause hyperthermia. 2. Tolerance gradually developed when arachidonate was administered repeatedly at intervals of 1‐7 days. Examination of the brains of several tolerant animals revealed in each case marked enlargement of the lateral ventricles which apparently accounted for the diminished response to arachidonate. 3. Sodium salicylate (40, 160 mg/kg, i.v.) antagonized arachidonate but only after a 3‐4 hr latent period. 4. Paracetamol (10, 40 mg/kg, i.v.) reduced the hyperthermic effect of arachidonate but a dose of 40 mg/kg antagonized centrally administered bacterial endotoxin more effectively than it did arachidonate. 5. Indomethacin (40 mug/kg, i.v.) significantly reduced arachidonate‐induced hyperthermia in only one of two studies. This reduction was comparable to the hypothermic effect of indomethacin in afebrile animals and was attributed to a non‐specific action on thermoregulatory function rather than to inhibition of prostaglandin synthesis. Indomethacin antagonized endotoxin and leucocytic pyrogen to a greater degree than it did arachidonate. 6. Comparison of the relative effectiveness of the antipyretics in blocking hyperthermic responses to pyrogens and to sodium arachidonate indicates that, if prostaglandins do mediate pyrogen‐induced fever, these antipyretics exert their primary at a step before prostaglandin synthesis.
Action of sympathetic nerves of inner and outer muscle of sheep carotid artery, and effect of pressure on nerve distribution.
Authors: Keatinge W R , Torrie C
Published: December 2014

1. The direction of torsion produced during active shortening of helical strips of sheep carotid arteries was measured to assess whether inner or outer muscle was contracting. 2. Noradrenaline contracted inner (non‐innervated) muscle in lower concentrations than were needed to contract outer (innervated) muscle, even with desipramine present to prevent uptake of noradrenaline by the nerves and with enough cyanide present to rise the normally low O2 tension of inner muscle to that of outer muscle. 3. Activation of sympathetic nerves in the outer part of the artery by nicotine caused almost evenly balanced contraction of both parts of the wall, with slight bias to outer contraction. 4. Moderate external constriction of the artery in vivo for 10‐17 days, in order to raise pressure throughout the wall to intraluminal pressure, made the entire wall nerve‐free. 5. The results provide evidence that the nerves can induce substantial activation of inner muscle, which is highly sensitive to noradrenaline, and that the absence of nerves from inner muscle can be explained by the high pressure there.
Maturation of the renal response to hypertonic sodium chloride loading in rats: micropuncture and clearance studies.
Authors: Baker J T , Solomon S
Published: December 2014

1. The ability of maturing rats to excrete a sodium load was studied by micropuncture and clearance procedures. 2. During control conditions, no change of glomerular filtration rate or sodium excretion was observed for the time period of the entire procedure (P greater than 0‐20). During the infusion of hypertonic (4%) sodium chloride, fractional sodium excretion was 0‐08 +/‐ 0‐01 in rats 21‐30 days old and 0‐14 +/‐ 0‐01 (P less than 0‐01) in adults. However, the depression of proximal tubular water re‐absorption was equal in both groups (P greater than 0‐20). 3. Proximal glomerulotubular balance for water re‐absorption was similar in all groups (P less than 0‐20). Since end proximal tubular water excretion and depression of fractional water excretion were the same in all animals, differences of urinary sodium excretion during development are probably due to differences of function of segments beyond the proximal tubule during development. 4. Fractional potassium excretion was reduced in young rats (0‐17 +/‐ 0‐04) during hypertonic sodium chloride infusion, compared to adults (0‐24 +/‐ 0‐01, P less than 0‐05). 5. Passage time of fast green through cortical segments in seconds is prolonged in young rats during control conditions. Similar decreases of passage time were seen in all groups during hypertonic sodium chloride infusion. No segmental differences of passage time were seen during developmental. 6. No difference in the relationship between fractional sodium and water excretion was seen during development of the renal response to hypertonic sodium chloride infusion. Thus, altered sensitivity to sodium chloride osmotic diuresis does not exist during maturation in rats.
The regulation of respiratory evaporative heat loss in the rabbit.
Authors: Stitt J T
Published: December 2014

1. Respiratory evaporative heat loss in the rabbit has a minimum value of 0‐2‐0‐3 W/kg and a maximum value of about 1‐1 W/kg in non‐evaporatively limited environments. 2. Both skin temperature and hypothalamic temperature influence respiratory evaporative heat loss, and they do so in a multiplicative fashion. Thus, at low skin temperature the hypothalamic temperature threshold for the onset of panting is above normal hypothalamic temperature and hypothalamic thermosensitivity is high. On the other hand, at high skin temperatures, the hypothalamic temperature threshold for the onset of panting is well below normal hypothalamic temperature, but hypothalamic thermosensitivity is greatly reduced. 3. The influence of mean skin temperature (Tsk) and hypothalamic temperature on respiratory evaporative heat loss (Eres) in the rabbit can be described by the equation: Eres=1‐1‐0‐08 (Tsk‐39‐7) (Thy‐42‐9) greater than or equal to 0‐3 W/kg. 4. Thus, the ability of a lowered mean skin temperature to increase the thermosensitivity of the hypothalamus in response to local temperature changes applies to heat loss mechanisms as well as heat production mechanisms. It is suggested that the characteristics of this peripheral input into the C.N.S. are fulfilled by tonic cold fibre input originating from the peripheral cold receptors on the body surface.
The negative potential wave evoked in cuneate nucleus by stimulation of afferent pathways: its origins and susceptibility to inhibition.
Authors: Andres-Trelles F , Cowan C M , Simmonds M A
Published: December 2014

1. The negative (N)‐wave evoked at various depths in the cuneate nucleus by stimulation of afferents in the ipsilateral forepaw or dorsal column has been studied in the rat. 2. Micro‐iontophoretic applications of gamma‐aminobutyric acid (GABA) into the vicinity of the recording electrode markedly reduced the amplitude of the negative wave, but only when recordings were made near the base of the cuneate nucleus. Nearer the surface of the medulla, GABA was much less effective. 3. A similar depth distribution obtained for the depression of the negative wave by micro‐iontophoretic Mg2+ and enhancement by Ca2+. 4. Depression of the negative wave by conditioning stimulation of the afferent pathway also showed a similar depth distribution. The conditioned depression of the negative wave was most marked during the first 30 ms after the conditioning stimulus and this early depression could be antagonized by iontophoretic (+)‐bicuculline methochloride. A lesser degree of conditioned inhibition of the negative wave persisted up to 80‐200 ms but this was resistant to (+)‐bicuculline methochloride. Thus, conditioned depression of the negative wave appeared to be mediated only in part by a GABA‐like transmitter. 5. It is concluded that the negative wave recorded near the base of the cuneate nucleus has some of the predicted properties of a post‐synaptic potential. These properties are not seen when the negative wave is recorded more superficially, near the surface of the medulla.
Studies on renin release from isolated superfused glomeruli: effects of temperature, urea, ouabain and ethacrynic acid.
Authors: Baumbach L , Leyssac P P , Skinner S L
Published: December 2014

1. The effects of different energy substrates, of low temperature, of urea, and of ouabain and ethacrynic acid were studied on the rate of renin release from viable juxtaglomerular cells during superfusion of isolated rat glomeruli. 2. Neither lactate nor glutamate altered renin release rate from that observed using glucose as the sole energy substrate. Succinate 10 mM elevated release transiently but did not influence the release caused by reductions in osmolality through lowering sucrose concentration. 3. Peak renin release was more prolonged and returned more slowly to control following reductions in osmolality in phosphate‐Ringer than in bicarbonate‐Ringer. 4. At 37 degrees C, the peak of renin released induced by hypo‐osmolality was smaller and delayed, and returned earlier to control than at 30 degrees C. Reduction in temperature from 30 to 4 degrees C resulted in a 32‐fold increase in basal release rate. At 4 degrees C a 20 m‐osmole/kg reduction in tonicity caused an additional 2‐5‐fold increase in release rate. 6. Increasing superfusate osmolality with urea did not affect basal renin release but 100 mM urea suppressed the releasing effect of a 15 mM reduction in NaCl concentration. 7. Ouabain (10(‐4) M) caused a small (33 +/‐ 9%, P less than 0‐025) transient increase in renin release. Ethacrynic acid (10(‐3) M) provoked a progressive increase in release reaching 100 +/‐ 15% above control within 50 min. In the presence of both inhibitors the release provoked by hyposmolality was prolonged. 8. It is concluded that renin release in vitro is a function of actively regulated cell volume and it is proposed that a similar mechanism could underline both barorecptor and macula densa controls of renin secretion in vivo.
A quantitative study of metiamide, a histamine H2‐antagonist, on the isolated whole rat stomach.
Authors: Bunce K T , Parsons M E
Published: December 2014

1. An isolated whole stomach preparation from immature rats is described. The lumen of the stomach was perfused and the hydrogen ion activity of the perfusate recorded continuously. 2. The mean basal acid secretion before stimulation was 4‐19 +/‐ 0‐31 X 10 (‐8) mol min‐1. Metiamide did not significantly reduce this spontaneous secretion. 3. The preparation gave dose‐dependent responses to histomine (10(‐5)‐10(‐4)M) which were readily reversed on washing. 4. The effect of metiamide on histamine‐stimulated acid secretion was investigated. Metamide, at doses of 3 X 10(‐6)M, and 3 X 10(‐5)M, caused a parallel displacement of the histamine dose‐response curve, indicating competitive antagonism. These dose‐response curves were used to calculate dose ratios (DR) for metiamide. 5. A plot of log10 (DR ‐ 1) against log 10 [antagonist] gave a pA2 value for metiamide of 5‐91.
Analysis of pace‐maker and repolarization currents in frog atrial muscle.
Authors: Brown H F , Clark A , Noble S J
Published: December 2014

1. A quantitative analysis of the time‐dependent component of outward membrane current in atrial wall trabeculae from Rana catesbeiana and Rana ridibunda has been carried out using a double sucrose gap technique. 2. Separation of the different components of delayed outward current was hampered by the sigmoid onset of one of the outward current systems ixfast and by the development of potassium ion accumulation which prevented current activation from reaching a steady state at positive membrane potentials. Semilogarithmic analysis of positive current decay tails recorded immediately following square voltage clamp depolarizations was therefore used to separate the two membrane conductance components ixfast and ixslow and the third component, attributable to potassium ion accumulation, which was almost invariably present in the tails. 3. It is shown that inaccuracies in this method of semilogarithmic separation of components caused by visual assessment of the i3 (accumulation) line are minor compared with the large changes in the time constants of ixfast and more especially of ixslow which would result from ignoring the potassium accumulation component. 4. Such semilogarithmic separation of the three components of outward current gave separate activation curves for each of the two membrane conductance components, ixfast and ixslow. 5. Measurement of 'total' activation curves in which all components of outward current were represented could be made more easily and fairly reliably. The position and shape of these activation curves on the voltage axis were found to closely resemble those obtained by three component separation. It is therefore suggested that such a simplified analysis reflects the properties of the individual currents sufficiently well for it to be of use in preliminary studies of, for example, drug action. 6. The kinetic properties of the atrial outward currents have been investigated over a wide potential range. Because of the presence of potassium ion accumulation, an indirect method of obtaining the average value of 1/gamma for outward current decay at negative potentials had to be employed. 7. It is shown that some degree of inward‐going rectification is associated with the outward current systems of frog atrium. 8. The possible reasons for the differences between the analysis presented here and those presented earlier by us (Brown & Noble, 1969a, b) and by Ojeda & Rougier (1974) are discussed.
Stimulus‐secretion coupling: role of cyclic AMP, cyclic GMP and calcium in mediating enzyme (kallikrein) secretion in the submandibular gland.
Authors: Albano J , Bhoola K D , Heap P F , Lemon M J
Published: December 2014

1. The role of adenosine 3':5'‐phosphate (cyclic AMP) and guanosine 3':5'‐phosphate (cyclic GMP) as second messengers for the enzyme secretory response evoked by the autonomic neurotransmitters, noradrenaline and acetylcholine, is examined in this in vitro study on the guinea‐pig submandibular gland. 2. Noradrenaline increased enzyme (kallikrein) secretion. The initial stimulation of enzyme release appeared to be dose‐dependent. The time course of cumulative kallikrein secretion revealed a complex pattern. Isoprenaline and phenylephrine were almost as potent as noradrenaline in releasing kallikrein. Both propranolol and phentolamine were required to fully inhibit the noradrenaline‐stimulated enzyme secretion. 3. The cumulative secretion of kallikrein evoked by acetylcholine was dose‐dependent. The onset of secretion showed a significantly greater time‐lag than that observed with noradrenaline. Atropine effectively blocked the release of kallikrein by acetylcholine. 4. Dibutyryl cyclic AMP stimulated enzyme secretion. Dibutyryl cyclic GMP caused an initial increase which was not maintained. 5. The cyclic nucleotide phosphodiesterase inhibitors, theophylline and papaverine, increased basal kallikrein secretion. The action of the cyclic phosphodiesterase inhibitors on the secretory response to noradrenaline, acetylcholine, dibutyryl cyclic AMP and dibutyryl cyclic GMP was complex. In general, the increase in enzyme release produced by the secretagogues was additively enhanced by both inhibitors. 6. Omission of calcium inhibited both acetylcholine and dibutyryl cyclic GMP stimulated kallikrein release, but to a lesser degree than that of noradrenaline and dibutyryl cyclic AMP. High concentrations of extracellular calcium (10 mM) appeared to enhance the action of acetylcholine. 7. Noradrenaline produced a rise in the intracellular level of cyclic AMP. The increase preceded the stimulated secretion of kallikrein. Of the various adrenergic agonists, noradrenaline and isoprenaline were the most potent, whereas phenylephrine was significantly less effective in raising basal cyclic AMP values. Acetylcholine was without effect, even in the presence of a cyclic phosphodiesterase inhibitor. 8. Acetylcholine and noradrenaline raised intracellular levels of cyclic GMP only when the tissue incubations were performed in the presence of a cyclic phosphodiesterase inhibitor. The increase in cyclic GMP produced by acetylcholine preceded enzyme secretion. 9. Morphological data substantiated the finding that the in vitro release of kallikrein evoked by the secretagogues was associated with the depletion of secretory granules and vacuolations in acinar cells of the gland slices. 10. The molecular mechanisms which control enzyme secretion in the exocrine submandibular gland are discussed. Models are presented for the role of transmitter‐specific cyclic nucleotides and calcium in stimulus‐secretion coupling.
Heat production and chemical change during isometric contraction of rat soleus muscle.
Authors: Gower D , Kretzschmar K M
Published: December 2014

1. Methods are described whereby the soleus muscle of the rat may be used for the investigation of initial processes in the absence of oxidative recovery. 2. The anaerobic conditions employed had no effect on the concentration of phosphocreatine in resting muscle or the mechanical response during contraction. 3. Muscles were stimulated tetanically for 10 s at 17‐18 degrees C. Measurements were made of the heat production and metabolic changes that occurred during a 13 s period following the first stimulus. 4. There was no detectable change in the concentration of ATP. Neither was there detectable activity of adenylate kinase or adenylate deaminase. The changes in the concentration of glycolytic intermediaries were undetectable or very small. 5. The change in the concentration of phosphocreatine was large and amounted to ‐127 +/‐ 11‐4 mumol/mmol Ct (mean and S.E. of the mean, negative sign indicates break‐down, Ct = free creatine + phosphocreatine) which is equivalent to about ‐2‐13 mumol/g wet weight of muscle. The heat production was 6549 +/‐ 408 mJ/mmol Ct (mean and S.E. of mean) which is equivalent to about 110 mJ/g. 6. About 30% of the observed energy output is unaccounted for by measured metabolic changes. 7. The ratio of heat production (corrected for small amounts of glycolytic activity) to phosphocreatine hydrolysis was ‐49‐7 +/‐ 5‐6 kJ/mol (mean and S.E. of mean), in agreement with previous results using comparable contractions of frog muscle, but different from the enthalpy change associated with phosphocreatine hydrolysis under in vivo conditions (‐34 kJ/mol). 8. The results support the notion that the discrepancy between energy output and metabolism is an indication of an unidentified process of substantial energetic significance that is common to a number of species.
The number of sodium ion pumping sites in skeletal muscle and its modification by insulin.
Authors: Erlij D , Grinstein S
Published: December 2014

1. [3H]ouabain binding by frog sartorius muscles shows at least two components: one linked to inhibition of the pump and another not related to transport inhibition. This is suggested by the finding that [3H]ouabain uptake continued to increase when (a) the glycoside concentration was increased beyond that causing maximum transport inhibition, and (b) exposure times longer than those required to produce full inhibition were used. 2. A number of 1600 pumping sites per mum2 of membrane was estimated considering only the cylindrical surface of the muscle. 3. Insulin stimulated the ouabain‐sensitive components of 22Na efflux and 134Cs influx. It also increased [3H]ouabain binding to a level of 1‐7 times the total resting value. The increases in [3H]ouabain binding and in 22Na efflux followed a similar relationship with respect to insulin concentration. 4. Insulin stimulated the Na pump in muscles whose pumping sites had been inhibited by ouabain and then transferred to a glycoside‐free solution. This stimulation was observed before detecting any recovery of the initial pumping activity. 5. When both the resting and the insulin‐stimulated 22Na efflux had been blocked by ouabain, an additional dose of insulin, in a ouabain‐free solution, had no further effects on 22Na efflux. 6. The effects of insulin were unaffected by cycloheximide or by high concentrations of butyryl derivatives of cyclic AMP and cyclic GMP. 7. We conclude that there are two pools of Na pumping sites in muscle cells: one active and another inactive. Insulin unmasks the inactive pumping sites by a mechanism that is independent of protein synthesis, increases in intracellular [Na] or decreases in intracellular [K].
The role of cyclic 3',5'‐adenosine monophosphate (cyclic AMP) in the ability of sympathetic nerve stimulation to enhance growth and secretion in rat salivary glands in vivo.
Authors: Muir T C , Templeton D
Published: December 2014

1. The cyclic AMP content of the rat salivary glands was measured after sympathetic and parasympathetic nerve stimulation, and after the administration of isoprenaline and phenylephrine. 2. Stimulation of the sympathetic nerves (20 Hz, 1 msec supramaximal voltage for 30 sec of every min) initially raised the cyclic AMP level in both the parotid and submaxillary glands. The rise, which was blocked by propranolol, was not maintained and declined during stimulation from the maximum (reached after 3 min stimulation) to control levels after approximately 15 min. Stimulation of the parasympathetic nerves for 5 min did not raise the cyclic AMP levels. 3. Isoprenaline and phenylephrine raised the cyclic AMP level in both glands. 4. Theophylline enhanced the growth of the parotid and submaxillary glands as measured either by an increase in the wet and dry weights or in acinar axes lengths. N6O2‐dibutyryl cyclic monophosphoric acid (dibutyryl cyclic AMP), did not enhance the growth of the glands. 5. It is concluded that cyclic AMP does not directly control cell growth in the rat salivary glands but may be a 'trigger' for events leading eventually to increased growth.
Activation of two types of fibres in rat extraocular muscles.
Authors: Chiarandini D J
Published: December 2014

1. The contractile responses of the inferior rectus, one of the extraocular muscles of the rat, to a depolarization induced by an elevation of the potassium concentration in the external medium ([K]O) have been studied 'in vitro'. 2. The elevation of [K]O to 20 and 30 mM‐K produced contractures that consisted of a sustained or tonic tension. When [K]O was increased to 50 mM or more a well‐defined transient or phasic tension appeared before the tonic response. The increment of [K]O above 50 mM enhanced the phasic component and depressed the tonic tension. The maximal tonic tension, usually evoked by 50 mM‐K, is about 50% of the tetanic tension, shows a gradual decline with time and lasts for hours. Control experiments performed in diaphragm showed that this muscle only responds with phasic tensions. 3. The difference in the repriming of the phasic and tonic responses when tensions were induced with salines containing low or normal [Cl] suggests that the muscle fibres responsible for the tonic tension are poorly permeable to Cl‐. 4. The amplitude of the tonic tension was reduced by Ca deprivation and by an elevation of [Ca] in the saline to 10 mM. 5. It is concluded that in rat extraocular muscles, an increase in [K]O activates two types of muscle fibres: singly and multiply innervated. These appear to be functionally equivalent to the twitch and slow fibres of amphibian and avian muscle and would give rise to the phasic and tonic components of the contracture, respectively.
The effects of very low external calcium and sodium concentrations on cardiac contractile strength and calcium‐sodium antagonism.
Authors: Miller D J , Moisescu D G
Published: December 2014

1. The tension levels of the contractures induced in frog atrial trabeculae by reduction of the bathing Na concentration have been investigated over a wide range of [Na+]o and [Ca2+]o, making use of EGTA to buffer [Ca2+]o under 10(‐5)M. 2. The relationship between tension and the quotient [Ca2+]o/[Na+]2o is only an apparent one, and holds approximately for Na concentrations as low as 1‐5 mM. 3. However, for low Na concentrations tension depends on the absolute values of both [Ca2+]o and [Na+]o. 4. Extracellular Ca is the essential factor in tension production. The results indicate an apparent threshold for tension near 5 X 10(‐8) M‐[Ca2+]o. 5. It can be shown that, under the present experimental conditions, the Na concentration around the cells must be lower than about 0‐1 mM in 'zero' Na+ solutions. 6. It is shown that the over‐all process leading to tension production can be explained in terms of a reaction involving two Ca ions. 7. To account for the results, a modification of the reaction scheme put forward by Lüttgau & Niedergerke (1958) is proposed, involving a competitive action between Ca and Na ions at a free receptor site. 8. To account for the scheme, an example of a mechanism involving both internal and external Na and Ca concentrations is considered.
Mechanosensitive afferent units in the hypogastric nerve of the cat.
Authors: Floyd K , Hick V E , Morrison J F
Published: December 2014

1. Recordings have been made from ninety single afferent units in the hypogastric and lumbar splanchnic nerves of the cat. 2. The majority of units examined had properties similar to those previously described in the splanchnic nerve: they were slowly adapting mechanoreceptors with one to six punctate mechanosensitive sites distributed mainly along blood vessels as they approached the viscera in peritoneal ligaments; they had a wide range of mechanical thresholds and conduction velocities in the range 0.5‐24 m s‐1. 3. Receptive fields were found over the bladder base or its peritoneal ligaments or both, on the uterus or broad ligament or both, on the colon or mesocolon or both, and in association with the ureter, vas deferens, prostate or pelvic fat pads. 4. Discharges from afferent units associated with the bladder were investigated during spontaneous (or reflex) bladder contractions, passive distensions, and tetanic contractions induced by electrical stimulation of the sacral spinal cord. The mean spike rates of the adapted (tonic) discharges, observed during distensions and induced tetani, differed over part of the range of intravesical pressures examined. Their behaviour is discussed in relation to the concept of 'in series' tension receptors within the bladder wall.
The effects of potassium and temperature on the pace‐maker current, iK2, in Purkinje fibres.
Authors: Cohen I , Daut J , Noble D
Published: December 2014

1. The reversal potential for the pace‐maker K current, iK2, was measured in sheep cardiac Purkinje fibres at extracellular K concentrations, [K]O, between 2‐7 and 8 mM. The reversal potentials were found to be significantly more negative than the values predicted using the Nernst equation for any reasonable value of intracellular K+ concentration or activity. 2. It is suggested that this discrepancy may be explained by postulating that the extracellular K+ concentration [K]e in the cleft spaces between cells is smaller than [K]o as a result of ion pumping and restricted diffusion from the bulk extracellular medium. 3. In conformity with this hypothesis, it was shown that the value of [K]e may be further reduced by hyperpolarizing pulses, presumably as a consequence of K+ depletion during the passage of inward current. 4. The influence of temperature on the kinetics of the gating mechanism, s, controlling iK2 was investigated. The Q10 for the time constant, pis, of current change following voltage clamp steps was found to be about 17. This corresponds to an apparent activation enthalpy of 50 kcal/mole. 5. The Q10 of the maximum amplitude iotaK2, was found to 1‐3. 6. The activation curve, s infinity (Em), spread slightly to more negative potentials by cooling from 37 to 30 degrees C and the curve became less steep. 7. There is a large decrease in the inward background current on cooling, as estimated by measuring the net membrane current when iK is presumed to be zero, i.e. at the reversal potential for iK2.
Induction of transporting sites in a sodium transporting epithelium.
Authors: Cuthbert A W , Shum W K
Published: December 2014

1. Frogs (Rana temporaria) were bathed for 1 week in solutions containing 1‐1 mM sodium chloride and either one or both of amiloride (10(‐4)M) and spironolactone (10(‐5r both of amiloride (10(‐4) M) and spironolactone (10(‐5) M). This procedure was designed to deplete the sodium transporting compartment of the skin epithelium of sodium, while at the same time antagonizing the effects of endogenous aldosterone. 2. After 1 week the skins were used in vitro to measure the level of sodium transport (short‐circuit current) and the density of sodium entry sites in the mucosal surface of the epithelium ([14C]amiloride binding). 3. Sodium deprivation for 1 week caused approximately a doubling of both sodium transport and the density of sodium entry sites in the mucosal surface of the epithelium compared to control skins. 4. When the results for sodium deprived and control skins were pooled there was a highly significant correlation between the density of sodium entry sites and sodium transport. 5. Mechanisms by which sodium deprivation leads to an increase in the density of sodium entry sites are discussed.
alpha‐Adrenergic, beta‐adrenergic and cholinergic mechanisms for amylase secretion by rat parotid gland in vitro.
Authors: Leslie B A , Putney J W , Sherman J M
Published: December 2014

1. Rat parotid gland slices, incubated in a balanced, buffered salt solution, were found to be physiologically stable for up to 2 hr with respect to O2 consumption, water content, extracellular space and cation content. 2. The slices could be stimulated to secrete amylase by activation of alpha‐adrenergic, beta‐adrenergic or muscarinic cholinergic receptors. 3. The secretion elicited through all three receptors appeared to involve exocytosis as revealed by electron microscopy. 4. The beta‐agonist, isoprenaline, increased tissue content of cyclic adenosine 3',5'‐monophosphate (cyclic AMP); alpha‐adrenergic and cholinergic agents had no effect on the level of this cyclic nucleotide. 5. Secretion via cholinergic or alpha‐adrenergic mechanisms required extra‐cellular calcium; the beta‐adrenergic mechanism did not. 6. It was concluded that stimulation of rat parotid cells activates distinctly separate pathways leading ultimately to exocytosis, one pathway involving cyclic AMP, and the other, external Ca2+ ion.
Possible presynaptic inhibition in rat olfactory cortex.
Authors: Pickles H G , Simmonds M A
Published: December 2014

1. Field potentials were evoked from rat olfactory cortex slices in vitro at room temperature by lateral olfactory tract stimulation. At very slow stimulation rates (less than 0‐1 Hz) a delayed negative wave (late N‐wave) was found to follow the first negative wave (N‐wave). This late N‐wave started 30 msec after the stimulus and lasted for 50‐150 msec. 2. Low Ca2+/high Mg2+ medium abolished the late N‐wave more rapidly than the N‐wave, suggesting a possible multisynaptic origin. 3. The GABA antagonist bicuculline (10(‐6) M) abolished the late N‐wave without affecting the N‐wave. 4. During the late N‐wave, both the tract action potential and the N‐wave to a second stimulus were reduced. This was attributed, at least in part, to collision with antidromic action potentials which could be detected during the late N‐wave. 5. These findings are discussed in terms of a possible presynaptic depolarizing action of a GABA‐like transmitter giving rise to presynaptic inhibition and the late N‐wave.
Increment sensitivity in humans with abnormal visual experience.
Authors: Beyerstein B L , Freeman R D
Published: December 2014

1. Visual acuity is lower for gratings oriented diagonally than for those of horizontal and vertical orientations. In addition to this oblique effect, some subjects show substantial deficits in acuity for horizontal or vertical targets (meridional amblyopia). These subjects are invariably astigmatic, but the condition has a neuronal basis and is thought to arise from faulty post‐natal neural development. 2. Foveal increment sensitivites have been determined for normal subjects and meridional amblyopes using bar‐shaped targets of various lengths, widths and orientations.3. Normal subjects do not exhibit differences in sensitivity as a function of orientation. No oblique effect is found for 1‐5' wide bars ranging in length from 10 to 60'. On the other hand, meridional amblyopes have substantial differences in increment sensitivity which depend on test target orientation. Invariably, when there is a deficit in acuity for a particular grating orientation, there is also a reduction in increment sensitivity for a bar of the same orientation. This effect is diminshed or eliminated when the background illuminance is lowered from 70 to 7td. 4. The orientational differences in increment sensitivity found in meridional amblyopes do not increases for bars longer than about 10'. As the bar is shortened, the differences are reduced, and they are absent when the test bar is 6' or less. 5. In normal subjects, for a 1 degree long bar, increment sensitivity increases with width up to about 4' where the width‐sensitivity curve levels off. No orientation differences are exhibited. Prominent orientation differences are found with meridional amblyopes when the bar target width is altered. The normal meridian is similar to those of the control subjects but the deficity meridian has very low sensitivity and summation is present for widths up to about 11'.
Oscillations in rod and horizontal cell membrane potential: evidence for feed‐back to rods in the vertebrate retina.
Authors: Normann R A , Pochobradský J
Published: December 2014

1. Rods and horizontal cells were studied with intracellular recordings in the retina of the toad, Bufo marinus; 161 cells were from the eyecup preparation and thirty were from the isolated perfused retina. 2. Of these cells, 39% exhibited either transient or sustained oscillations of membrane potential. Light flashes either evoked transient oscillations or temporarily abolished sustained oscillations. The amplitudes of the oscillations could be as large as 27 mV. The frequency of the oscillations at 25 degrees C was between 1‐5 and 3‐5 Hz and was strongly dependent on temperature and background illumination. 3. The rod oscillation amplitude and the peak of the horizontal cell light response increased similarly with increasing test flash diameters. They continued to grow for diameters much larger than those which increased the peak of the rod light response. 4. Perfusion of the isolated retina with 2 mM aspartate had only a small effect on the rod light response but it completely eliminated the horizontal cell light response as well as the oscillations recorded in both rods and horizontal cells. 5. It is believed that the oscillations result from a reverberating interaction between rods and neurones post‐synaptic to rods. Thus, rods can be both post‐ as well as presynaptic retinal elements.