bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of narcotic analgesics and their antagonists on the rabbit isolated heart and its adrenergic nerves
Authors: MONTEL H. , STARKE K. 
Published: July 2012

Summary
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

Summary
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.
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.