bluuebunny/crossref_metadata_2025 huggingface dataset:
The metabolic effects, and the composition of the tissue lost, in weight reduction by obese patients on treatment with fenfluramine
Authors: DURNIN J. V. G. A. , WOMERSLEY J.
Published: July 2012

Three groups of obese patients were treated for periods of up to 6 months. One group of 52 individuals received 80–120 mg fenfluramine daily. The second group of 20 people had placebo tablets. The third group of 28 patients were on a dietary restricted régime.

Only the fenfluramine and dietary treated groups lost weight but there was no evidence of an increased metabolic rate after fenfluramine, either at rest or in standardized exercise. During the first month of treatment the mean weight loss in the group treated with fenfluramine was greater than that in the group treated by diet alone, but the difference was not significant (P<0·05). By the third month of treatment the mean weight loss was smaller in both groups, particularly in the women.

The composition of the tissue lost in the weight reduction had a mean fat content of 75% and did not differ significantly between the fenfluramine group and the diet‐restricted group, except in women.
Localization of the central cardiovascular action of clonidine
Authors: BOUSQUET P. , GUERTZENSTEIN P. G.
Published: July 2012

The fall in arterial blood pressure with bradycardia that occurs on injection of clonidine into the cerebral ventricles and into the cisterna magna is attributed to an action on ‘chemosensitive zones’ situated at the ventral surface of the brain stem. This conclusion is based on the following results obtained in cats anaesthetized with pentobarbitone sodium.

The fall in blood pressure no longer occurs on injection of clonidine (10 to 100 μg) into the cerebral ventricles when the passage of clonidine into the subarachnoid space is prevented by cannulation of the aqueduct. In this condition, the injections produce instead a rise in blood pressure.

Applied bilaterally, by means of perspex rings, to the ventral surface of the brain stem, clonidine (10 μl of a 50 to 1,000 μg/ml solution placed in each ring) produces a fall in blood pressure with bradycardia, but only when the perspex rings cover the ‘chemosensitive zones’ from which changes in blood pressure and heart rate are obtained with various drugs.
Effects of narcotic analgesics and their antagonists on the rabbit isolated heart and its adrenergic nerves
Authors: MONTEL H. , STARKE K.
Published: July 2012

In isolated perfused hearts of rabbits, the effects of morphine, methadone, pethidine, fentanyl, levallorphan and naloxone on heart rate, the spontaneous outflow of noradrenaline, the uptake of infused noradrenaline and the overflow of noradrenaline in response to stimulation of the accelerans nerves were investigated.

At concentrations of 10–100 μm, methadone, fentanyl, levallorphan and naloxone, but not morphine and pethidine, decreased the heart rate. Only pethidine and levallorphan (100 μm) augmented the spontaneous outflow of noradrenaline.

With the exception of naloxone, all drugs diminished the neuronal uptake of noradrenaline from the perfusion fluid. Methadone and pethidine (1 μm) were the most effective inhibitors. The inhibitory effect of morphine was not antagonized by naloxone.

All drugs increased the overflow of noradrenaline evoked by stimulation of the accelerans nerves at 5 Hz. Simultaneously, the positive chronotropic effect of stimulation was usually enhanced. Morphine also augmented the response to stimulation at 2·5 and 10 Hz. The effect of morphine was prevented by pre‐infusion of cocaine. The response to stimulation was never depressed.

It is concluded that the adrenergic nerves of the rabbit heart lack specific morphine receptors which in some other sympathetic nerves mediate an inhibition of the stimulation‐induced secretion of noradrenaline. The mechanism of the enhancement of adrenergic neurotransmission by relatively high concentrations of the drugs is discussed.
Kinetics of the release of noradrenaline from micropipettes: interaction between ejecting and retaining currents
Authors: BRADSHAW C. M. , ROBERTS M. H. T. , SZABADI E.
Published: July 2012

The role of ejecting and retaining currents in determining the kinetics of the release of [14C]‐noradrenaline (NA) from micropipettes of the type used in microelectrophoresis experiments has been investigated by the liquid scintillation counting technique.

In the absence of any electrophoretic current a constant rate of release of NA was established.

All retaining currents examined gradually reduced the spontaneous release to zero. Higher retaining currents abolished spontaneous release more quickly.

A linear relationship was identified between the rate of electrophoretic release of NA and the intensity of the ejecting current. The mean transport number of NA was found to be 0·17.

All retaining currents studied reduced the amount of NA released during a subsequent application of an ejecting current. This was due to a prolongation of the time necessary to establish a steady‐state rate of release. The magnitude of this effect was related to both the intensity and the duration of application of the retaining current.

The results are discussed in terms of a theoretical model of ion movements within the tip of the micropipette.
INHIBITION OF THE PROSTAGLANDIN SYNTHETASE SYSTEMS IN OCULAR TISSUES BY INDOMETHACIN
Authors: BHATTACHERJEE P. , EAKINS K.E.
Published: July 2012

We have compared the sensitivity of the prostaglandin synthetase systems derived from microsomal fractions of rabbit ocular tissues (anterior uvea, conjunctiva and retina) with other rabbit tissues such as the kidney medulla and spleen, to inhibition by indomethacin.

Generation of prostaglandin‐like activity by the microsomal fractions from added arachidonic acid varied with the tissue used. Highest activity was found in the kidney medulla, then in descending order, the conjunctiva, anterior uvea, spleen, retina and cornea.

Indomethacin was most potent in the spleen (ID50 0.045 μg/ml) then in decreasing order in the kidney medulla, conjunctiva, anterior uvea and weakest in the retina, where the ID50 for indomethacin was 50 μg/ml.

The differential sensitivity to inhibition of the prostaglandin synthetase systems from different tissues is an important consideration in the development of new ocular anti‐inflammatory agents.
DIFFERENCES IN AMINE STORAGE IN RAT HEART AND BRAIN
Authors: ENNA S.J. , SHORE P.A.
Published: July 2012

The characteristics of storage of amphetamine‐releasable amine in rat heart and brain were studied in vitro with labelled and unlabelled metaraminol ([3H]‐MA and MA).

In one series of experiments, heart and brain slices were incubated with [3H]‐MA prior or subsequent to incubation with the same concentration of MA.

When brain slices, thus treated, were subjected successively to field stimulation and to amphetamine, it was found that the ratio of [3H]‐MA release by field stimulation to release by amphetamine was dependent upon the order in which brain tissue was exposed to [3H]‐MA and MA.

With heart slices, on the other hand, the field stimulation/amphetamine ratio of [3H]‐MA release remained the same whether the tissue was exposed to [3H]‐MA before or after MA.

The (+)‐isomer of amphetamine released three to four times more [3H]‐MA from brain slices than did the (–)‐isomer, while the isomers were equipotent with regard to [3H]‐MA release from heart slices.

Amphetamine‐induced [3H]‐MA release from heart slices was unaffected by the presence of α‐methyl‐p‐tyrosine, while release from brain slices was inhibited.

On the basis of the foregoing results it appears that amine storage differs in brain and heart, with brain exhibiting more than one functional amine pool.
DOSE‐RESPONSE CURVES FOR ANGIOTENSIN II AND SYNTHETIC ANALOGUES IN THREE TYPES OF SMOOTH MUSCLE: EXISTENCE OF DIFFERENT FORMS OF RECEPTOR SITES FOR ANGIOTENSIN II
Authors: PAPADIMITRIOU A. , WORCEL M.
Published: July 2012

The dose‐response curves for angiotensin II and four analogues in rat colon and uterus, and in rabbit aorta, were obtained.

The ED50 values of angiotensin II as well as the ED50s and intrinsic activities of angiotensin analogues varied between the three organs.

The interaction of two competitive antagonists with angiotensin II receptors was also examined. The KI values obtained with both antagonists on the uterus differed from the values on the other tissues.

It is concluded that angiotensin II receptors may be different in the three organs examined.
INDOLEAMINE ANTAGONISTS: RELATIVE POTENCIES AS INHIBITORS OF TRYPTAMINE‐ AND 5‐HYDROXYTRYPTOPHAN‐EVOKED RESPONSES
Authors: CLINESCHMIDT B.V. , LOTTI V.J.
Published: July 2012

Four indoleamine antagonists were evaluated for relative potencies as inhibitors of tryptamine‐induced forepaw clonus and 5‐hydroxytryptophan‐evoked head twitches. Methergoline was approximately three times more potent against the forepaw clonus than the head twitch response, whereas methysergide exhibited nearly equal activity in both tests. Cyproheptadine and cinanserin showed a profile opposite to methergoline and a greater degree of selectivity, being 25 to 40 times more potent as inhibitors of the 5‐hydroxytryptophan‐ than of the tryptamine‐induced response. These findings clearly demonstrate that the rank order of potency of indoleamine antagonists varies greatly depending upon the test procedure employed.
ADENOSINE TRIPHOSPHATE‐INDUCED CONTRACTILE PROCESS IN RAT LYMPHOCYTES AND ITS INHIBITION BY ANTI‐INFLAMMATORY AGENTS
Authors: GÖRÖG P. , KOVÁCS IREN B.
Published: July 2012

Addition of adenosine triphosphate to glycerol‐treated rat lymphocytes produced characteristic cytoplasmic movements. These were inhibited or prevented by low concentrations of acetylsalicylic acid, phenylbutazone and indomethacin.
PHARMACOLOGY OF M & B 18,706, A DRUG WHICH SELECTIVELY REDUCES DECEREBRATE RIGIDITY
Authors: MAXWELL D.R. , READ M.A. , SUMPTER EILEEN A.
Published: July 2012

(±)‐10‐(3‐Dimethylamino‐2‐methylpropyl)‐2‐valeroylphenothiazine hydrochloride (M & B 18,706) has been compared with dimethothiazine, chlorpromazine, diazepam and baclofen for potency in reducing decerebrate rigidity in the cat and rat and for activity in causing ataxia or sedation.

When given intravenously M & B 18,706 had seven times the potency of dimethothiazine and one‐half the potency of chlorpromazine in reducing the rigidity of the intercollicular decerebrate cat. When administered orally M & B 18,706 and chlorpromazine were equi‐potent in reducing rigidity but M & B 18,706 was less effective than chlorpromazine in producing ataxia in this species.

In the rat, M & B 18,706 had one‐quarter the potency of chlorpromazine for reducing decerebrate rigidity but had from 1/20th to 1/200th its potency in tests for sedative or tranquillizing activity.

M & B 18,706, like dimethothiazine and chlorpromazine, had little effect on the rigidity of ischaemic decerebrate cats and failed to inhibit polysynaptic spinal reflexes.

M & B 18,706 had intravenous potency comparable to chlorpromazine in reducing the pressor action of noradrenaline in the spinal cat.
MORPHINE AND NEUROTRANSMITTER SUBSTANCES: MICROIONTOPHORETIC STUDY IN THE RAT BRAIN STEM
Authors: BRADLEY P.B. , DRAY A.
Published: July 2012

The effects of microiontophoretically applied morphine and its interactions with the effects of microiontophoretic applications of either acetylcholine, (–)‐noradrenaline or 5‐hydroxytryptamine have been studied on single neurones in the brain stem of rats anaesthetized with urethane.

Morphine excited or inhibited most neurones tested and the effects, especially excitation, were often extremely powerful. However, the time course of the excitatory and inhibitory effects were somewhat different.

Desensitization to the excitation produced by morphine was seen after repeated or prolonged applications and it is suggested that this phenomenon may be related to the tolerance which develops after chronic administration of morphine. No desensitization was observed to inhibition of neuronal activity by morphine.

Morphine usually reduced the excitation of neurones by acetylcholine, noradrenaline or 5‐hydroxytryptamine but sometimes potentiated the effect, although not always on the same neurones. Inhibition of neuronal activity by these compounds was never modified by morphine and neither were the effects of glutamate or D,L‐homocysteic acid when used as control agonists.

The in vitro release of morphine from six micropipettes was determined and the transport number was calculated to be 0.051 (s.d. 0.021).

The implications of these observations in explaining the pharmacological actions of morphine are discussed.
TRANSMISSION TO THE LONGITUDINAL MUSCLE OF THE GUINEA‐PIG VAS DEFERENS: THE EFFECT OF PRETREATMENT WITH GUANETHIDINE
Authors: FURNESS J.B.
Published: July 2012

Tissue was taken from guinea‐pigs that had been injected with guanethidine (100 mg/kg, i.p.) 24 h before they were killed, and from paired control animals.

Pretreatment with guanethidine caused a significant, substantial, and sometimes complete reduction of the nerve‐mediated contractions of the vas deferens. There were no significant changes in the responses of the ileum to stimulation of cholinergic nerves or of the distal colon to stimulation of intrinsic (non‐adrenergic) inhibitory nerves. Responses of the vas deferens and ileum to acetylcholine were unchanged, but contractions of the vas deferens elicited by exogenous noradrenaline were enhanced.

The nerve‐mediated contractions of the vas deferens were restored by exposing it to (+)‐amphetamine followed by noradrenaline in vitro.

It is concluded that noradrenaline is the transmitter released from motor nerves to the longitudinal muscle of the guinea‐pig vas deferens. Possible explanations for the ineffectiveness of receptor blocking agents in antagonizing transmission are discussed.
STUDIES ON THE TACHYPHYLAXIS TO NICOTINIC STIMULANT DRUGS IN THE PERFUSED HYPOGASTRIC GANGLION OF THE GUINEA‐PIG
Authors: BENTLEY G.A.
Published: July 2012

The guinea‐pig hypogastric ganglion, perfused through its vasculature with physiological saline solutions, will respond repeatedly to nicotinic stimulant drugs injected at 4 min intervals into the perfusion stream. Stimulation is indicated by contraction of the vas deferens. After a varying number of doses of nicotinic stimulants, complete tachyphylaxis usually develops, and normally this persists for at least 1 hour. During this time, however, electrical stimulation of the hypogastric nerve is still fully effective.

Tachyphylaxis may be reversed for varying periods of time by all of the following procedures: (a) tetanic stimulation of the hypogastric nerve; (b) injection of large doses of histamine, methacholine, or potassium chloride; (c) perfusion with saline containing ouabain 0.1 μg/ml or 80–100 mm lithium chloride, or, to a lesser extent, with potassium‐free saline.

Tachyphylaxis is always re‐established with further doses of nicotinic stimulants, except during perfusion with lithium solutions.

Atropine hastens the onset of tachyphylaxis, but does not prevent its reversal by hypogastric nerve stimulation or by histamine or potassium. However, it does prevent the reversal by methacholine and by lithium.

Tachyphylaxis occurs in decentralized ganglia, and can be reversed by histamine, methacholine, and by tetanic stimulation of the hypogastric ganglion. Hence tachyphylaxis and its reversal cannot be due to an effect on presynaptic fibres.

Potassium chloride stimulates the ganglion both before and after tachyphylaxis has developed to nicotinic drugs, and hence this is unlikely to be due to a depolarization block.

It is concluded that tachyphylaxis could be due to a prolonged ganglionic hyperpolarization.
CALCIUM DEPENDENCE OF THE INHIBITORY EFFECT OF ANGIOTENSIN ON RENIN SECRETION IN THE ISOLATED PERFUSED KIDNEY OF THE RAT
Authors: VAN DONGEN R. , PEART W.S.
Published: July 2012

The effect of calcium on the inhibition of renin secretion by biologically active angiotensin was investigated in the isolated rat kidney perfused with Krebs‐Ringer saline.

In the presence of calcium (3.7 mm), asp(NH2)′‐angiotensin II suppressed both basal and isoprenaline‐stimulated renin secretion. Renal perfusion pressure, which was increased by the infusion of angiotensin, returned to control levels when isoprenaline was added.

When the calcium concentration was reduced to 0.32 mm, the vasoconstriction produced by angiotensin was abolished although the inhibitory effect on renin secretion was still evident.

In the absence of calcium, angiotensin no longer suppressed basal renin secretion and a prompt increase in renin secretion occurred when isoprenaline was added.

The higher basal renin levels which were observed in calcium‐free perfusions, suggest the existence of an intrarenal calcium‐dependent mechanism that regulates basal renin secretion.

These observations indicate that the inhibitory effect of biologically active angiotensin, on basal and isoprenaline‐stimulated renin secretion, is functionally related to the contractor response by its dependence on calcium. The recognition that the renin‐producing cells are modified smooth muscle cells supports this association
THE RABBIT RECTOCOCCYGEUS: A GANGLION‐FREE, PARASYMPATHETICALLY INNERVATED PREPARATION
Authors: AMBACHE N. , KILLICK S.W. , ZAR M. ABOO
Published: July 2012

Isolated, desheathed preparations of the rabbit rectococcygeus muscle were relatively insensitive to spasmogens other than muscarinic drugs. Transmural stimulation with 1–50 pulses (0.2–0.4 ms at 10 Hz) elicited graded twitches which were abolished by tetrodotoxin and were therefore neurogenic; longer pulses sometimes triggered tetrodotoxin‐resistant myogenic contractions.

Twitches elicited by 0.2–0.4 ms pulses were due to post‐ganglionic excitation because they were not reduced by hexamethonium, pentolinium or dimethyltubocurarine, or by ganglion‐paralyzing concentrations of nicotine.

The acetyl‐ and butyryl‐cholinesterase activities of the rectococcygeus were determined manometrically and could be selectively inhibited by BW 284C51 (1:5‐bis‐(4‐allyl‐dimethyl‐ammonium‐phenyl)‐pentan‐3‐one dibromide) and iso‐OMPA (tetramonoisopropylpyrophosphortetramide), respectively. Single‐pulse twitches were greatly potentiated in amplitude and duration only when both cholinesterases were inhibited.

The preparations could not be made to contract by nicotine (2.1–21 μm) even after cholinesterase inhibition, suggesting an absence of ganglion‐cells; with nicotine (105–210 μm) small, atropine‐susceptible responses were elicited, which were non‐ganglionic because they were not reduced by tetrodotoxin.

Rectococcygeus preparations that had been treated with physostigmine released acetylcholine into the bath fluid on electrical stimulation.

The motor transmission was paralyzed by botulinum toxin (Type A) and abolished by atropine; the block of muscarinic receptors by atropine was effective against both endogenous and exogenous acetylcholine.

Inhibitory adrenoceptors and scanty motor α‐adrenoceptors were detected in the smooth muscle.

Strong inhibitions of motor transmission and of rhythmic activity were produced by noradrenaline (but not by tyramine), by isoprenaline, and, after phentolamine, also by adrenaline and phenylephrine. These inhibitions were only slightly reduced by propranolol and rather more by pindolol.

Experiments on preparations retaining their extrinsic nerve supply suggest an absence of ganglionic relays in the last 1–2 cm of the motor nerve pathway to this muscle.

Some contrasting properties of the adjacent caudo‐anal muscle, including the poor motor responses to transmural stimulation, are described.
EFFECT OF SYMPATHOMIMETIC AMINES ON THE HISTAMINE FORMING CAPACITY OF HUMAN LEUCOCYTES
Authors: ASSEM E.S.K.
Published: July 2012

The effects of α‐ and β‐adrenoceptor stimulants on the histamine‐forming capacity (HFC) of human isolated leucocytes have been studied, in vitro.

It was confirmed that antigen significantly stimulates the HFC of human leucocytes.

β‐Adrenoceptor stimulants, such as isoprenaline and salbutamol (10−6‐10−3 m) significantly inhibited the HFC of human leucocytes in the presence and absence of antigen. At concentrations lower than 10−6 m, this effect was not observed. In general the degree of inhibition of HFC by β‐adrenoceptor stimulants followed their potency as β‐adrenoceptor stimulants.

α‐Adrenoceptor stimulants significantly stimulated leucocyte HFC; noradrenaline within a limited concentration of 10−6 m, while stimulation was seen consistently with phenylephrine at concentrations of 10−7‐10−4 m. Adrenaline, which stimulates both α‐ and β‐adrenoceptors, produced small inhibition, no effect, or a degree of stimulation.

Phentolamine, an α‐adrenoceptor blocking agent, produced an effect opposite to that of the α‐adrenoceptor stimulants, i.e. a significant inhibition of the HFC of human isolated leucocytes.
EVIDENCE OF CHOLECYSTOKININ RELEASE BY BOMBESIN IN THE DOG
Authors: ERSPAMER V. , IMPROTA G. , MELCHIORRI P. , SOPRANZI N.
Published: July 2012

The intravenous infusion of bombesin elicited in the dog a contraction of the gall bladder with decreased opening pressure of the choledocho‐duodenal junction and stimulation of pancreatic secretion.

The pancreatic juice produced under the influence of bombesin was poor in bicarbonate and rich in protein. Threshold doses of the peptide were of the order of 0.25 μg kg−1 h−1 and maximum protein output was obtained with 1 μg kg−1 h−1. The pancreatic protein response to bombesin was very similar, in its onset and duration, to that elicited by intraduodenal infusion of l‐tryptophan. Infusions of bombesin repeated at short intervals produced tachyphylaxis.

Antrectomy did not affect the stimulant action of bombesin on the pancreas. Atropine however, reduced the pancreatic protein response to bombesin.

It is suggested that bombesin acts on the gall bladder and the exocrine pancreas through release of cholecystokinin from the duodenal mucosa. No release of secretin could be demonstrated. It is likely that the releasing activity of bombesin is limited, in the field of gastrointestinal peptides, to those belonging to the gastrin‐cholecystokinin family.
TRANSPORT OF TAURINE BY NORMAL HUMAN BLOOD PLATELETS
Authors: AHTEE LISA , BOULLIN D.J. , PAASONEN M.K.
Published: July 2012

Because normal human blood platelets contain higher concentrations of taurine than any other amino acid, and have a platelet: plasma concentration gradient exceeding 400:1, we isolated the cells in vitro and incubated them with radioactively labelled taurine in order to investigate the existence of a metabolically‐dependent accumulation process.

Platelets incubated with taurine (1 to 100 nmol/ml) in autologous plasma or Krebs solution accumulated [14C]‐taurine against the concentration gradient.

The transport process was saturable at high concentrations, showed a requirement for sodium ions, and was temperature‐dependent.

The kinetics of transport fulfilled the criteria of Michaelis & Menten for saturable enzyme/substrate interactions, but the kinetic constants were influenced by the incubation medium.

The metabolic inhibitors 2,4‐dinitrophenol and iodoacetic acid in combination inhibited taurine transport in Krebs solution, but stimulated transport in autologous plasma. The latter result suggested the involvement of a sodium‐dependent ATPase in taurine transport.

We conclude that platelets actively transport taurine in vitro under experimental conditions closely resembling those likely to occur in vivo, and that this taurine transport process may be involved in the maintenance of the platelet: plasma concentration gradient.
THE EFFECT OF CHLORPROPAMIDE ON WATER BALANCE IN PITRESSIN‐TREATED BRATTLEBORO RATS
Authors: LAYCOCK J.F. , LEE J. , LEWIS A.F.
Published: July 2012

The daily administration of a 5% glucose solution to the heterozygous Brattleboro rat produced an experimental model in a comparable state of polydipsia and polyuria to the homozygous rat with diabetes insipidus (DI).

The effect of chlorpropamide on water metabolism was then examined in both the homozygous DI rat treated with sub maximal doses of pitressin tannate in oil (Pitressin), and in the glucose‐hydrated heterozygous rat with and without simultaneous pitressin therapy.

A dose‐response curve for chlorpropamide (5, 10, and 20 mg/24 h) in DI rats treated with Pitressin (25 mu/24 h) indicated that the drug decreased fluid intake further, but only by a maximum of 13.8% (at the 20 mg/24 h dose of chlorpropamide), differing markedly from results obtained in patients with diabetes insipidus. A second experiment in which chlorpropamide (5 mg/24 h) was administered to DI rats treated with Pitressin (either 25 or 50 mu/24 h) confirmed the lack of any significant drug‐effect on water metabolism in these animals.

Chlorpropamide (20 mg/24 h), when administered alone or simultaneously with a submaximal dose of Pitressin (25 mu/24 h), had no obvious effect on the fluid intake of glucose‐hydrated heterozygous rats. The absence of any action by chlorpropamide on water metabolism was confirmed in these experimental animals using 5 mg/24 h of the drug together with Pitressin (either 25 or 50 mu/24 hours).

Indirect evidence for the slower growth‐rate in the DI rat being due to an insufficient daily calorific intake was obtained from the study on glucose‐hydrated heterozygous rats.
β‐ADRENOCEPTOR BLOCKING AGENTS AND RESPONSES TO ADRENALINE AND 5‐HYDROXYTRYPTAMINE IN RAT ISOLATED STOMACH AND UTERUS
Authors: SCHECHTER YAEL , WEINSTOCK MARTA
Published: July 2012

Four β‐adrenoceptor blocking agents, (±)‐ and (+)‐propranolol, practolol and oxprenolol, were found to antagonize, apparently competitively, the responses of both the rat isolated stomach and uterus to 5‐hydroxytryptamine (5‐HT).

The pA2 values for each of these agents as antagonists of the contractile action of 5‐HT on the rat stomach were found to be: (±)‐propranolol, 6.08; (+)‐propranolol, 4.94; practolol, 3.43; and oxprenolol, 5.99. These values were very similar to the corresponding figures for antagonism of 5‐HT‐induced contractions of the uterus.

pA2 values for antagonism of adrenaline‐induced relaxations by the four blocking agents on the rat stomach and uterus did not differ from the values for 5‐HT blockade.

To antagonize contractile responses to acetylcholine of the rat stomach it was necessary to give 100 times more (±)‐propranolol than was needed to antagonize responses to 5‐HT.
DRUG‐INDUCED CHANGES IN CAPILLARY FILTRATION COEFFICIENT AND BLOOD FLOW IN THE INNERVATED SMALL INTESTINE OF THE ANAESTHETIZED CAT
Authors: RICHARDSON P.D.I.
Published: July 2012

A modification of the Folkow Technique for simultaneous measurement of blood flow and capillary filtration coefficient (CFC) in the cat jejunum is described. The modification retained the sympathetic innervation of the preparation, and in the present experiments, drugs were administered intravenously.

There is evidence that CFC is a cardiovascular quantity independent of blood flow or regional vascular resistance in these preparations. Low doses of drugs may affect CFC without altering the blood pressure, blood flow, or heart rate.

Under control conditions the CFC, a measure of functional exchange vessel area, was lower than previously reported for similar, but denervated preparations.

α‐Adrenoceptor stimulation with phenylephrine (1.0 μg kg−1 min−1, i.v.) caused a fall of 75–85% from control values of CFC with concomitant rises in blood pressure of 0–15% and falls in blood flow of 10–40%. The heart rate rose by 0–15%. Phentolamine (0.5–2.0 mg/kg, i.v.) caused a rise in CFC and a slight fall in vascular resistance, and blocked the effects of phenylephrine on this tissue.

β‐Adrenoceptor stimulation with isoprenaline (0.2 μg kg−1 min−1, i.v.) caused a rise in CFC of 75–110%, a fall in blood pressure of 0–10%, a rise in blood flow of 10–60% and a rise in heart rate of up to 35%. Propranolol caused a transient rise in CFC when injected i.v. in a dose of 0.1 mg/kg, which was adequate to block the effects of isoprenaline.

Angiotensin (25–100 ng kg−1 min−1, i.v.) caused falls in CFC of up to 100% and rises in vascular resistance. Aminophylline (0.2–0.4 mg kg−1 min−1, i.v.) caused rises in CFC of up to 200% with falls in vascular resistance.

Histamine (0.01 to 1.0 μg kg−1 min−1, i.v.) had little effect on vascular resistance, but 10 and 40 μg kg−1 min−1 caused falls in vascular resistance. Doses up to and including 10 μg kg−1 min−1 caused falls in CFC, but the higher doses, or smaller doses after histaminase inhibition caused rises in CFC. α‐Adrenoceptor blockade reversed the fall in CFC caused by small doses of histamine, to a rise. Mepyramine completely blocked the effects of histamine on these preparations.

5‐Hydroxytryptamine (33–100 μg kg−1 min−1, i.v.) caused a rise in vascular resistance and a fall in CFC of up to 85%. These effects were blocked by methysergide (250 μg/kg, i.v.).

Rises in CFC indicate an increase in functional exchange vessel area in the tissue, and falls in CFC a decrease in the area available for vascular exchange. These changes are examined against the possibility of the drugs causing reflex adjustments in sympathetic tone, of systemic deactivation of intravenously administered drugs, and of drug effects on vascular permeability.
THE RELEASE OF LABELLED ACETYLCHOLINE AND CHOLINE FROM CEREBRAL CORTICAL SLICES STIMULATED ELECTRICALLY
Authors: RICHARDSON I.W. , SZERB J.C.
Published: July 2012

In order to establish the origin of the increased efflux of radioactivity caused by electrical stimulation of cerebral cortical slices which had been incubated with [3H]‐choline, labelled choline and acetylcholine (ACh) collected by superfusion were separated by gold precipitation.

In the presence of physostigmine electrical stimulation (1 Hz, 10 min) increased the release of only [3H]‐ACh which was greatly enhanced by the addition of atropine.

Continuous stimulation in the presence of physostigmine resulted in an evoked release of [3H]‐ACh which declined asymptotically. This evoked release appeared to follow first‐order kinetics with a rate constant which remained stable over the course of prolonged stimulation.

The rate constant for the evoked release of [3H]‐ACh with 1 Hz stimulation was three times greater in the presence of physostigmine and atropine than in the presence of physostigmine alone, while the size of the store from which [3H]‐ACh was released was nearly identical under these two conditions.

In the absence of physostigmine and atropine, stimulation caused the appearance of only [3H]‐choline in the samples.

Reduction of [3H]‐ACh stores before the application of physostigmine resulted in a reduced evoked release of total radioactivity, both in the absence or presence of physostigmine and atropine, and decreased the evoked release of [3H]‐ACh without affecting the release of [3H]‐choline.

Results suggest that electrical stimulation of cortical slices which had been incubated with [3H]‐choline causes the release of only [3H]‐ACh, both in the presence or absence of an anticholinesterase. The evoked increase in the efflux of total radioactivity is therefore a good measure of the release of [3H]‐ACh.
THE EFFECT OF NERVE STIMULATION ON THE AXONAL TRANSPORT OF NORADRENALINE AND DOPAMINE‐β‐HYDROXYLASE
Authors: KEEN P. , McLEAN W.G.
Published: July 2012

A method for stimulating the lumbar sympathetic outflow from the spinal cord of the rat is described which does not require artificial respiration of the animal.

In some, but not all experiments continuous stimulation at 2 Hz or intermittently at 10 Hz accelerated the rate at which noradrenaline and dopamine‐β‐hydroxylase accumulated central to a ligature on the sciatic nerve by approximately 40%.

It is concluded that, although nervous activity is not necessary for axonal transport of transmitter granules in sympathetic neurones, intense nervous activity may accelerate the rate of granule transport.
THE INNERVATION OF THE RATCERVIX AND ITS PHARMACOLOGY In vitro AND In vivo
Authors: HOLLINGSWORTH M.
Published: July 2012

Contractions of the rat cervix and uterine horns were measured both in vitro and in vivo as changes in luminal perfusion pressure during perfusion at constant flow.

Spontaneous cervical and uterine horn contractions in vitro were reduced from rats pre‐treated with 17β‐oestradiol compared to those ovariectomized only or those pre‐treated with 17β‐oestradiol plus progesterone.

The rat cervix exhibited similar in vitro sensitivities to methacholine, oxytocin, isoprenaline and phenylephrine as did the uterine horns.

Transmural stimulation produced cervical and uterine horn contractions, which were blocked by hyoscine or tetrodotoxin, suggesting a cholinergic motor innervation. This was supported by histological findings.

In vivo, the injections of propranolol (1.9 × 10−7 mol/kg) or pempidine (3.2 or 6.4 × 10−6 mol/kg) were followed by large cervical and smaller uterine horn contractions, suggesting an adrenergic inhibitory tone mediated by β‐adrenoceptors.

The evidence for a cervical sphincter is discussed.
EFFECTS OF ADRENALINE, NORADRENALINE, ISOPRENALINE AND SALBUTAMOL ON THE PRODUCTION AND RELEASE OF RENIN BY ISOLATED RENAL CORTICAL CELLS OF THE CAT
Authors: JOHNS E.J. , RICHARDS H.K. , SINGER BERTHA
Published: July 2012

Isolated renal cortical cells of the cat have been demonstrated to produce renin on incubation in vitro. After 2 h of incubation, without added agonist, the total amount of renin in the flask increased by a mean of 27.2%. The increase in renin content of the incubation flask was found to be present in the medium.

Noradrenaline (1.18 × 10−4 M) and adrenaline (1.09 ×; 10‐4 M) added to the incubation medium stimulated renin production by 45 and 34% respectively, compared with the incubated controls. Most of the increase in renin production was present in the incubation medium.

Isoprenaline did not stimulate renin production. However, when added to the incubation medium at a concentration of 0.72 × 10‐4 M there was a significant decrease in the cellular content and a significant increase in the medium content of renin. This increase was at least as great as that observed with adrenaline and noradrenaline.

Salbutamol had an effect similar to isoprenaline, i.e. it induced the release of renin into the medium without affecting production. In this respect it was about a third as potent as isoprenaline.
STIMULATION OF THE HYPOTHALAMO‐PITUITARY‐ADRENAL AXIS BY COMPOUNDS FORMED IN INFLAMED TISSUE
Authors: LEME J. GARCIA , SCHAPOVAL ELFRIDES E.S.
Published: July 2012

Rat paws were injected with carrageenin, and their subcutaneous tissue perfused 135 min later. These perfusates were injected intravenously into receptor rats in which they caused an attenuation of inflammatory responses.

The effect was not observed in adrenalectomized receptor rats nor in receptors with electrolytic lesions in the median eminence of the hypothalamus but persisted in adrenal‐demedullated animals.

The active perfusates also induced eosinopenia in normal or adrenal‐demedullated animals, but not in adrenalectomized rats, and produced an increase in blood corticosterone with a concomitant decrease in the amounts of adrenal ascorbic acid.

The active perfusates did not affect the responses of isolated preparations to histamine, bradykinin, prostaglandins and 5‐hydroxytryptamine neither did they elicit changes of the arterial blood pressure in receptor animals.

The anti‐inflammatory activity present in perfusates from inflamed paws seems to be formed slowly at the site of the developing inflammatory reaction, since perfusates collected 30‐65 min after the injection of carrageenin were ineffective, as was plasma taken from donor rats at various time intervals after carrageenin injections.

It is suggested that the anti‐inflammatory factor present in the active perfusates exerts its action by stimulation of the hypothalamo‐pituitary‐adrenal axis.
THE POSSIBLE OCCURRENCE OF ENDOGENOUS ANTI‐INFLAMMATORY SUBSTANCES IN THE BLOOD OF INJURED RATS
Authors: ATKINSON D.C. , HICKS R.
Published: July 2012

Using the carrageenin rat paw oedema test as an assay, an attempt has been made to confirm the presence of anti‐inflammatory activity in the blood of rats with a chronic inflammatory lesion induced by a polyester sponge, and to relate such activity to the systemic anti‐inflammatory effect exerted in situ by the lesion. In addition, plasma from rats given acetic acid intraperitoneally has been examined for anti‐inflammatory properties.

The activity of serum obtained from sponge‐bearing adrenalectomized Wistar rats did not differ significantly from that obtained from animals without implants. Furthermore, implanted sponges exerted no systemic anti‐inflammatory effect.

Similar experiments were performed in sponge‐bearing adrenalectomized Sprague‐Dawley rats, plasma instead of serum being examined for anti‐inflammatory activity. The plasma removed from such animals possessed no anti‐inflammatory activity, whilst implanted sponges exerted a small, yet significant, systemic inhibitory effect.

When the irritancy of sponge implants was augmented with croton oil, more marked systemic anti‐inflammatory effects were observed. However, the plasma obtained from rats injured in this manner exerted no anti‐inflammatory effect.

No anti‐inflammatory activity could be detected in plasma samples obtained from rats treated with doses of acetic acid capable of producing pronounced systemic anti‐inflammatory effects.

It was concluded that the induction of these inflammatory lesions in rats does not appear to lead to a detectable release of endogenous anti‐inflammatory substances into the circulation.
USE OF THE LOGISTIC FUNCTION FOR THE CALCULATION OF DOSE‐RATIOS AND POTENCY RATIOS
Authors: BARLOW R.B.
Published: July 2012

Dose‐ratios and potency ratios, obtained with the guinea‐pig isolated ileum by calculating matching concentrations from a least‐squares fit using a logistic relationship between response and dose, differ from those obtained with the more usual assumption that response is a linear function of log dose over a limited range.

The differences are not due to the mathematical treatment of the results but arise from changes in sensitivity associated with the production of very high or very low responses.

With this preparation there is no advantage in avoiding the linear transformation and fitting the results to the complete dose‐response curve though this might not apply to results obtained from other tissues with less variable sensitivity.
THE ESTIMATION OF 3,4‐DIHYDROXYPHENYLACETIC ACID, HOMOVANILLIC ACID AND HOMO‐lSOVANILLIC ACID IN NERVOUS TISSUE BY GAS‐LIQUID CHROMATOGRAPHY AND ELECTRON CAPTURE DETECTION
Authors: PEARSON J.D.M. , SHARMAN D.F.
Published: July 2012

A gas chromatographic method using electron capture detection is described for the estimation of three acidic metabolites of dopamine, 4‐hydroxy‐3‐methoxyphenylacetic acid (homovanillic acid, HVA), 3,4‐dihydroxyphenylacetic acid (DOPAC) and 3‐hydroxy‐4‐methoxyphenylacetic acid (homo‐isovanillic acid, iso‐HVA). The method is based on the formation of the trifluoroacetyl‐hexafluoroisopropyl derivatives of the three acids.

The method has been applied to the estimation of DOPAC, HVA and iso‐HVA in tissues from the central and peripheral nervous systems.
THE EFFECT OF OXYTOCIN ON BLOOD VESSELS OF CREMASTER MUSCLE OF THE RAT
Authors: ELLIOTT ANNIE B.
Published: July 2012

Oxytocin administered intravenously to the anaesthetized rat produced dilatation of the blood vessels of the cremaster muscle at concentrations ranging from 2.5 × 10−11 to 2.5 × 10−9 M. When applied topically to the exposed vessels it produced constriction at concentrations ranging from 2.5 × 10−12 to 5.0 × 10−8 M. Oxytocin was thus similar to adrenaline in eliciting opposite effects when applied to the serosa or to the intima of skeletal muscle blood vessels.
KINETICS AND SOME CHARACTERISTICS OF UPTAKE OF NORADRENALINE BY THE HUMAN UMBILICAL ARTERY
Authors: GULATI O.D. , SIVARAMAKRISHNA N.
Published: July 2012

The uptake of exogenously added noradrenaline (NA) (0.5‐2.5 μg/ml) by the human umbilical artery was linear with time up to 10 minutes. The uptake was saturable and could be described by the Michaelis‐Menten equation. The uptake was cocaine‐resistant, normetanephrine‐sensitive, was considerably inhibited in the cold and was partially inhibited by Na+ ‐ deficiency. Of NA accumulated in the artery 31% could be washed out by NA‐free medium. It is concluded that the mechanism of uptake of NA by the human umbilical artery is similar to the uptake2 mechanism.
PROSTAGLANDIN PRODUCTION BY A MILD INFLAMMATORY LESION IN SHEEP
Authors: GREENWOOD B. , KERRY P.J.
Published: July 2012

By implanting a Teflon chamber subcutaneously into a sheep a mild aseptic inflammatory lesion was produced from which wound fluid could be sampled daily. The prostaglandin content of this wound fluid was examined. Prostaglandin E2 activity was found in all samples, and a peak was apparent on the fourth or fifth day after producing the lesion. The amount of prostaglandin activity appeared to be unrelated to the total number of polymorphs in the fluid or to the volume of this exudate.
VASOPRESSIN RELEASE BY NICOTINE: THE SITE OF ACTION
Authors: BISSET G.W. , FELDBERG W. , GUERTZENSTEIN P.G. , SILVA M. ROCHA E.
Published: July 2012

In cats anaesthetized with chloralose the release of neurohypophysial hormones was examined after injection of nicotine into the cerebral ventricles or cisterna magna or its topical application through perspex rings to the ventral surface of the brain stem. The release was measured by assaying the hormones in samples of venous blood

Injected into a lateral or the third cerebral ventricle, nicotine (0.5 to 1 mg) produced release of vasopressin without oxytocin. When the aqueduct was cannulated, preventing access to the fourth ventricle and to the subarachnoid space, this release did not occur.

Vasopressin was also released without oxytocin when nicotine (0.25 to 2 mg) was injected into the subarachnoid space through the cisterna magna. With this route of administration the nicotine did not enter any part of the ventricular system.

Applied through paired perspex rings placed across the ventral surface of the brain stem, nicotine again produced release of vasopressin without oxytocin. The amount of nicotine placed in each ring was usually 80 μg, but a release was obtained with 10 μg and in one experiment with as little as 5 μg.

The bilateral region on the ventral surface of the brain stem where nicotine acts when producing release of vasopressin lies lateral to the pyramids and in a longitudinal direction, 6 to 9 mm caudal to the trapezoid bodies.

The vasopressin release by nicotine injected intraventricularly or intracisternally, or applied topically to the ventral surface of the brain stem was not due to absorption of nicotine into the blood stream, nor to blood pressure effects.

It is concluded that nicotine acts on the ventral surface of the brain stem probably by activating the central projection to the supra‐optic and possibly also the paraventricular nuclei of afferent pathways in the sinus and vagus nerves which control the release of vasopressin in response to changes in blood volume or distribution.
THE EFFECTS OF LYSERGIC ACID DIETHYLAMIDE ON THE RESPONSE TO FIELD STIMULATION OF THE RAT VAS DEFERENS AND THE RAT AND CAT ANOCOCCYGEUS MUSCLES
Authors: GILLESPIE J.S. , McGRATH J.C.
Published: July 2012

The effect of lysergic acid diethylamide (LSD) on the response to field stimulation in vitro of the rat vas deferens and anococcygeus muscle was examined.

LSD in concentrations from 10−9 to 10−6 M caused an increase in tone or rhythmic activity in both tissues, effects identical to those produced by guanethidine or tyramine. The motor effects of all three drugs were abolished by phentolamine 2 × 10−6 M. Methysergide 2 × 10−7 M given before LSD reduced the motor effect but was ineffective once the LSD contraction had developed.

LSD 10−9 to 10−6 M reduced and eventually abolished the response to motor adrenergic nerve stimulation in the anococcygeus muscle with no effect on the response to noradrenaline (NA) and no evidence of differential sensitivity according to the number of stimulating pulses. In the vas deferens LSD abolished the initial twitch component with no effect on the secondary slow contraction. LSD had no effect on the response to inhibitory nerve stimulation in the anococcygeus.

These results suggest that in the anococcygeus LSD closely resembles guanethidine in its effects as an adrenergic neurone blocking drug with indirect sympathomimetic actions. In the vas deferens these properties would explain the block of the initial twitch component in the motor response to field stimulation and the increase in rhythmic activity but do not explain the resistance of the secondary slow component of the motor response.
REDUCTION OF ANTIGEN‐INDUCED CONTRACTION OF SENSITIZED HUMAN BRONCHUS in vitro BY INDOMETHACIN
Authors: DUNLOP LYN S. , SMITH A.P.
Published: July 2012

Contraction of passively sensitized human bronchus induced by antigen challenge in vitro, was reduced by the prostaglandin F2α synthetase inhibitor, indomethacin.

Prostaglandin F2α was released during challenge and this release was inhibited by indomethacin.

There was a significant correlation between prostaglandin F2α release and antigen challenge‐induced contraction, suggesting that this substance may contribute to the bronchoconstrictor response of sensitized human bronchus to antigen.
THE ROLE OF H1 AND H2‐RECEPTORS IN THE CORONARY VASCULAR RESPONSE TO HISTAMINE OF ISOLATED PERFUSED HEARTS OF GUINEA‐PIGS AND RABBITS
Authors: BROADLEY K.J.
Published: July 2012

The effects of histamine on the isolated perfused hearts of guinea‐pigs and rabbits were examined. Records of contractile force, heart rate and coronary perfusion pressure were obtained.

Histamine exerted positive inotropic and chronotropic effects which were antagonized by burimamide and attributed to stimulation of H2‐receptors.

The coronary vascular response to histamine differed between guinea‐pigs and rabbits. In guinea‐pig hearts, three phases were apparent: (a) An initial vasodilatation preceding any effects on heart force and rate was antagonized by mepyramine and therefore mediated by histamine H1‐receptors in the coronary circulation. (b) A secondary vasoconstriction was attributed to the increased myocardial compression during the positive inotropic and chronotropic responses. (c) The final, more predominant, component was a prolonged vasodilatation probably associated with the increased metabolic activity of the heart.

The latter two components were abolished together with the myocardial responses by burimamide. The remaining coronary vascular response was biphasic, consisting of a vasodilatation immediately followed by vasoconstriction. Both were antagonized by mepyramine and therefore mediated by H1‐receptors.

The coronary vascular response of rabbit hearts was similar but no direct vasodilatation was observed and it was concluded that histamine receptors in the coronary vasculature involve only vasoconstriction.
DOPAMINE‐INDUCED AMYLASE SECRETION FROM GUINEA‐PIG SUBMANDIBULAR GLAND
Authors: BLOOM G.D. , CARLSÖÖ B. , DANIELSSON Å.
Published: July 2012

The effects of dopamine, 5‐hydroxydopamine (5‐OHDA) and noradrenaline on amylase secretion from the guinea‐pig submandibular gland were investigated under in vitro conditions.

All three amines greatly enhanced amylase secretion. Blockade of dopamine β‐hydroxylase did not inhibit the response to dopamine.

Noradrenaline and dopamine stimulated amylase release from salivary glands of reserpine‐treated animals, whereas 5‐OHDA had no stimulatory effect on secretion in guinea‐pigs pretreated with reserpine.

Haloperidol completely inhibited dopamine‐induced enzyme discharge, but did not affect noradrenaline‐initiated secretion.

Apomorphine caused a slight enzyme release by itself; it diminished the dopamine secretory effect, but did not modify that of noradrenaline.

Pimozide and fluspirilene attenuated the dopamine‐induced enzyme discharge, but compared with haloperidol they were less effective.

It is concluded that dopamine exerts a secretagogic action different from that of noradrenaline. The possible presence of a specific dopamine receptor in salivary glands is discussed.