bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECTS OF α‐ AND β‐ADRENOCEPTOR ACTIVATION ON TENSION AND MEMBRANE PROPERTIES OF THE LONGITUDINAL SMOOTH MUSCLE OF THE CHICKEN RECTUM
Authors: KOMORI S. , OHASHI H. , TAKEWAKI T. 
Published: July 2012

Isolated longitudinal muscle strips from the chicken rectum responded to isoprenaline, adrenaline and noradrenaline with a prolonged relaxation. The concentrations required to produce 50% of the maximum relaxation were 1.3 times 10−8 m for isoprenaline, 1.7 times 10−8 m for adrenaline and 10−6 m for noradrenaline. The relaxing potency of isoprenaline is about equal to that of adrenaline, but more than 50 times that of noradrenaline.
Propranolol, 3.4 times 10−6 m, blocked the isoprenaline‐induced relaxation, and in the presence of this drug the responses to adrenaline and noradrenaline were converted into small, transient relaxations. The residual relaxation was blocked by phentolamine, 2.6 times 10−6 m.
These catecholamines suppressed spontaneous spike discharge and produced membrane hyperpolarization. Propranolol, 3.4 times 10−6 m, prevented the inhibitory effects of isoprenaline, and reduced but did not completely abolish those of adrenaline and noradrenaline.
Adrenaline and noradrenaline, but not isoprenaline, reduced membrane resistance in some preparations.
In the rectal muscle of the chicken, the β‐adrenoceptor mediates a prolonged relaxation and the α‐adrenoceptor a fast and short‐lasting relaxation which is usually obscured by the β‐response and unmasked only after blockade of the β‐adrenoceptors. The α‐ and β‐mediated relaxations are each associated with the suppression of spontaneous spike activity.
CALCIUM IONOPHORE A23187 INDUCES RELEASE OF CHEMOKINETIC AND AGGREGATING FACTORS FROM POLYMORPHO‐NUCLEAR LEUCOCYTES
Authors: BRAY M.A. , FORD‐HUTCHINSON A.W. , SHIPLEY M.E. , SMITH M.J.H. 
Published: July 2012

Rat and human polymorphonuclear leucocytes (PMNs) when exposed to calcium ionophore A23187 10 μm release products which cause aggregation of rat PMNs and chemokinesis of human PMNs.
Aggregating and chemokinetic activities are rapidly generated; maximal release occurs after 4 min, and can be detected in dilutions of the supernatant of up to 1:1000.
Generation of aggregating and chemokinetic activities is inhibited by nordihydroguaiaretic acid 10−4 to 10−7 m, 5,8,11,14‐eicosatetraynoic acid 10−4 and 10−5 m, BW 755C 10−4 m and benoxaprofen 10−4 m, all compounds known to inhibit lipoxygenase pathways of arachidonic acid (AA) metabolism.
Conventional non‐steroidal anti‐inflammatory agents, such as aspirin and indomethacin, inhibited little or not at all the generation of these activities.
We conclude that the aggregating and chemokinetic activities induced by A23187 represent generation of biologically active products of lipoxygenase pathways of AA metabolism.
PREJUNCTIONAL ACTIONS OF PIRIBEDIL ON THE ISOLATED KIDNEY OF THE RABBIT: COMPARISON WITH APOMORPHINE
Authors: CHEVILLARD C. , MATHIEU M.N. , RECOMMIS D. 
Published: July 2012

The effects of piribedil on contractile responses and noradrenaline release evoked by sympathetic nerve stimulation have been studied in the isolated kidney of the rabbit. These effects were compared to those of apomorphine.
Electrical stimulation (2, 5 and 10 Hz) of sympathetic renal nerves produced frequency‐dependent increases in perfusion pressure and noradrenaline release. Piribedil did not affect (0.1 μg/min) or diminished (1 and 10 μg/min) the stimulation‐evoked increase in perfusion pressure, and increased noradrenaline release in a dose‐dependent manner.
Increases in renal perfusion pressure and noradrenaline release induced by electrical stimulation were decreased by apomorphine (0.1 and 1 μg/min). These inhibitory effects were more marked at low frequencies of stimulation and were prevented by haloperidol (0.2 μmol/1).
Piribedil (0.1 and 1 μg/min) and apomorphine (0.1, 1 and 10 μg/min) did not affect the increases in renal perfusion pressure elicited by exogenously administered noradrenaline, but piribedil (10 μg/min) diminished them.
In the presence of desipramine (0.5 μmol/1), piribedil (0.1, 1 and 10 μg/min) produced a dose‐dependent inhibition of the increases in renal perfusion pressure and noradrenaline release evoked by sympathetic nerve stimulation; the inhibitory effect of piribedil was more marked at low frequencies of stimulation and was prevented by haloperidol.
Piribedil increased the resting release of noradrenaline from the rabbit kidney, in contrast to apomorphine, which was without effect.
It is suggested that piribedil has a complex effect on sympathetic transmission. This drug exhibits an ‘amphetamine‐like’ action, causing noradrenaline release from its postganglionic stores. This releasing effect masks an action on prejunctional inhibitory dopamine receptors. In addition, at high doses, piribedil exhibits a marked action on postjunctional sites, since it reduces the vasoconstrictor effect of exogenous noradrenaline.
EFFECTS OF INTRACEREBROVENTRICULAR FLOCTAFENINE AND INDOMETHACIN ON BODY TEMPERATURE IN FEBRILE RABBITS
Authors: LABURN HELEN , MITCHELL D. , STEPHEN J. 
Published: July 2012

We injected the potent prostaglandin synthesis inhibitors, floctafenine and indomethacin, intravenously and intracerebroventricularly in rabbits made febrile by intravenous injection of leucocyte pyrogen.
Floctafenine (75 μmol) injected intravenously failed to affect the fever, whereas indomethacin (15 μmol) markedly reduced the fever.
When injected into the cerebral ventricles, floctafenine was feebly antipyretic, and then only at a dose ten times the antipyretic dose of indomethacin.
Our results support the suggestion that floctafenine has no antipyretic action when administered peripherally. However, its lack of antipyretic effect cannot be explained solely on the grounds that it fails to cross the blood‐brain barrier.
THE POTENT DEPOLARIZING ACTION OF PALYTOXIN ISOLATED FROM Palythoa Tubercurosa ON THE ISOLATED SPINAL CORD OF THE FROG
Authors: KUDO YOSHIHISA , SHIBATA SHOJI 
Published: July 2012

The effects of palytoxin (PTX) isolated from Palythoa tubercurosa were tested on the isolated intra‐arterially perfused spinal cord of the frog. The resting and evoked potentials were recorded by means of a sucrose‐gap technique.
PTX caused a marked depolarization of both ventral and dorsal roots. The minimum effective concentration was extremely low, approximately 10−11 m. During the depolarization the evoked ventral and dorsal root potentials were markedly reduced in amplitude. The ventral root reflex was first augmented and then decreased.
The depolarization caused by PTX was markedly reduced when the preparation was perfused with NaCl ‐deficient medium. However, tetrodotoxin (10−7 m) only slightly inhibited the depolarization.
In a high Ca2+ medium (3.6 mm), the time required to reach the maximum depolarization evoked by PTX was significantly prolonged. In contrast, in a low Ca2+ medium (0.9 mm), PTX caused a marked depolarization soon after application. In a Ca2+‐free, Mg2+ (9.0 mm) medium, PTX caused rhythmic oscillatory potentials in both ventral and dorsal roots.
The potency of N‐acetyl PTX was one hundredth that of the parent compound.
It is suggested that PTX may interfere with the stabilizing action of Ca2+ on the neuronal membrane, consequently facilitating Na+ permeability. The primary amine in the PTX molecule may be important for its pharmacological action.
PHAGOCYTOSIS STIMULATES THE RELEASE OF A SLOW REACTING SUBSTANCE IN CULTURED MACROPHAGES
Authors: BRETZ U. , DEWALD B. , PAYNE T. , SCHNYDER J. 
Published: July 2012

A slow‐reacting substance (SRS) was released from non‐elicited mouse peritoneal macrophages during phagocytosis of zymosan particles, whereas no detectable SRS was produced by resting cells.
The macrophage SRS induced a delayed and slow contraction of the guinea‐pig ileum but not of the chick rectum.
The myotonic activity was antagonized by low concentrations of FPL 55712 (sodium 7‐[3‐(4‐acetyl‐3‐hydroxy‐2‐propylphenoxy)‐2‐hydroxypropoxy]‐4‐oxo‐8‐propyl‐4H‐1‐benzopyran‐2 carboxylate) but was not affected by mepyramine or hyoscine, and was not associated with tachyphylaxis.
SRS release was increased by indomethacin and was abolished by the lipoxygenase and cyclo‐oxygenase inhibitor, BW755C (3‐amino‐1‐[m‐(trifluoromethyl)‐phenyl]‐2‐pyrazoline).
Addition of exogenous arachidonic acid or cysteine enhanced SRS production.
AN ELECTROPHYSIOLOGICAL ANALYSIS OF THE EFFECTS OF NORADRENALINE AND α‐RECEPTOR ANTAGONISTS ON NEUROMUSCULAR TRANSMISSION IN MAMMALIAN MUSCULAR ARTERIES
Authors: HOLMAN MOLLIE E. , SURPRENANT ANNMARIE 
Published: July 2012

The effects of exogenously applied noradrenaline (NA) and α‐adrenoceptor antagonists on the mechanical and intracellularly recorded responses to perivascular nerve stimulation were examined in the rabbit ear artery, rabbit saphenous artery and rat tail artery.
Excitatory junction potentials (e.j.ps) and action potentials recorded from these smooth muscles were not blocked or depressed by phentolamine, phenoxybenzamine, prazosin, or labetolol in concentrations as high as 10 μg/ml. Phentolamine (1 to 10 μg/ml) depressed neurally‐evoked contractions of the ear and saphenous, but not the tail artery, and also depressed the contractions produced by direct muscle stimulation in the ear and saphenous arteries. Prazosin and labetolol (0.1 to 10 μg/ml) had no effect on the neurally evoked contractile response in any of the arteries examined.
The amplitude of the steady‐state e.j.p. during repetitive stimulation at 0.45 to 2 Hz was increased by phentolamine or phenoxybenzamine but not by prazosin or labetolol. Phentolamine and phenoxybenzamine also increased the amplitude of the e.j.p. evoked by a single stimulus in the majority of the preparations.
Concentrations of NA ≥ 1 μg/ml depolarized the smooth muscle while concentrations ≥ 0.5 μg/ml depressed the amplitude of the e.j.ps recorded from these arteries. α‐Antagonists did not suppress either the NA‐induced membrane depolarization or depression of e.j.ps.
These observations call into question the physiological relevance of both pre‐ and postsynaptic α‐receptors in regard to adrenergic neuromuscular transmission in muscular arteries.
EFFECT OF PROLONGED β‐ADRENOCEPTOR BLOCKADE ON HEART WEIGHT AND ULTRASTRUCTURE IN YOUNG RABBITS
Authors: NAYLER WINIFRED G. , SLADE A. , WILLIAMS E.M. VAUGHAN , YEPEZ CARMEN E. 
Published: July 2012

Young rabbits were treated for 30 days or 6 weeks with propranolol or oxprenolol to provide dose‐levels similar to those used clinically.
Relative to litter matched controls the treated rabbits exhibited a reduced rate of growth.
Morphometric studies showed that prolonged β‐adrenoceptor blockade had no effect on the myofibrillar volume as a proportion of cell volume.
Prolonged β‐blockade increased the proportion of the extracellular space occupied by vascular tissue.
THE EFFECTS OF PROPRANOLOL AND ACEBUTOLOL ON LEFT VENTRICULAR FUNCTION AND CORONARY HAEMODYNAMICS IN THE CONSCIOUS DOG WITH MYOCARDIAL ISCHAEMIA
Authors: HILLIS W.S. , HUTTON I. , LAWRIE T.D.V. 
Published: July 2012

The cardiovascular effects of the β‐adrenoceptor blocking drugs, propranolol and acebutolol, on regional coronary blood flow and left ventricular function have been investigated in the conscious dog with developing myocardial infarction.
Propranolol (1 to 1.5 mg/kg) or acebutolol (4 to 5 mg/kg) were administered intravenously 2 to 3 h after occlusion of the left anterior descending coronary artery.
Propranolol or acebutolol administration resulted in a relative increase in flow to the ischaemic area of the myocardium, particularly to the subendocardium.
Propranolol produced a greater reduction in heart rate and myocardial contractility than acebutolol.
These results demonstrate that β‐adrenoceptor blocking drugs reduce myocardial oxygen consumption and increase coronary flow to the ischaemic area of the myocardium after coronary artery occlusion in the conscious dog.
ACUTE EFFECTS OF MORPHINE AND OPIOID PEPTIDES ON THE MOTILITY AND RESPONSES OF RAT COLON TO ELECTRICAL STIMULATION
Authors: GILLAN MAUREEN G.C. , POLLOCK DAVID 
Published: July 2012

Morphine and leucine‐ and methionine‐enkephalins inhibited the contractile response of the pithed rat colon to electrical stimulation of the spinal motor outflows and inhibited motor responses of the isolated colon to field stimulation.
Morphine and the opioid peptides also had an excitatory action in the colon. In the pithed rat, opiates caused regular fluctuations in intracolonic pressure and in the isolated colon, caused regular waves of contraction. This excitatory response was produced by low concentrations of the enkephalins (2 × 10−8 m, 2 × 10−9 m), was stereospecific and was antagonized by naloxone.
Opiate‐induced contractions in the isolated colon were inhibited by catecholamines, adenine nucleotides and by phosphodiesterase inhibitors. These contractions were unaffected by ergotamine and tolazoline, or by propranolol.
The excitatory action of opiates in the isolated colon was not antagonized and usually was potentiated by atropine, (+)‐tubocurarine and hexamethonium. In the absence of opiates, these drugs also produced similar waves of contraction, which were unaffected by naloxone.
Opiate‐induced contractions occurred in colon rendered unresponsive to 5‐hydroxytryptamine (5‐HT) and these contractions were potentiated by the 5‐HT antagonist, lysergic acid diethylamide, which, when administered alone, caused similar contractions. The 5‐HT antagonist, cyproheptadine, inhibited opiate‐induced contractions but was non‐specific, since it also inhibited responses of the colon to carbachol and KCl.
Opiate‐induced contractions were unaffected by procaine and were potentiated by tetrodotoxin. Both of these drugs, when administered alone, produced waves of contractions, which were similar to those produced by opiates but were unaffected by naloxone.
Contractions produced in the isolated colon either by opiates, atropine or (+)‐tubocurarine, or any combination of these drugs, were inhibited by field stimulation applied at the peak of a wave of contraction. This inhibitory response to field stimulation occurred at low frequencies of stimulation (< 10 Hz), and persisted in colon from rats pretreated with reserpine to deplete, or 6‐hydroxydopamine to destroy, adrenergic nerve endings. It was unaffected by guanethidine but abolished by tetrodotoxin.
The implications of these results are considered and it is concluded that the excitatory action of opiates in the rat colon is probably not mediated by the release of acetylcholine or 5‐HT but instead, may be due either to a direct action on smooth muscle or to a presynaptic inhibitory action at a ganglionic site in a non‐adrenergic inhibitory mechanism, which normally suppresses myogenic activity.
A POSSIBLE NEGATIVE FEEDBACK CONTROL OF EXCITATORY TRANSMISSION VIA PROSTAGLANDINS IN CANINE SMALL INTESTINE
Authors: NAKAHATA N. , NAKANISHI H. , SUZUKI T. 
Published: July 2012

Contractile responses of canine intestinal circular and longitudinal muscles to field stimulation (20 Hz, 1 ms, 30 V/cm, for 5 s) were inhibited by treatment with atropine (0.1 μg/ml), indicating that the response to field stimulation was mediated by acetylcholine (ACh).
Prostaglandins E1 (PGE1), PGE2 and PGF2α inhibited the response of circular but not longitudinal muscle to field stimulation, althouth PGF2α was less effective than PGE1 and E2.
PGE1 was much less active in inhibiting the response of circular muscle to ACh than to field stimulation, suggesting that prostaglandins might act predominantly at prejunctional sites to prevent the release of ACh.
Indomethacin (1 μg/ml) potentiated the response of circular muscle but not longitudinal muscle to field stimulation.
Release of PGE‐like compounds from circular muscle only, was increased by field stimulation at 20 Hz (total of 1000 pulses) and ACh (10 μg/ml), but not by a lower frequency (2 Hz, total of 2400 pulses) which produced only a slight contraction. This finding may indicate that prostaglandins were released predominantly from the muscle.
Prostaglandins may exert a negative feedback mechanism of excitatory transmission in circular muscle but not in longitudinal muscle of canine small intestine.
INHIBITION BY MORPHINE OF PROSTAGLANDIN E1‐STIMULATED SECRETION AND CYCLIC ADENOSINE 3′,5′‐MONOPHOSPHATE FORMATION IN THE RAT JEJUNUM in vivo
Authors: BEUBLER E. , LEMBECK F. 
Published: July 2012

The effects were studied of prostaglandin E1 (PGE1), theophylline and morphine on net water flux and mucosal cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) levels in the jejunum of anaesthetized rats in vivo.
Infusion of PGE1 (3.2 μg/min, i.a.) caused a reversal from net water absorption to net secretion and enhanced the mucosal cyclic AMP content by 54%.
Theophylline (5 mg/ml, intraluminal) similarly produced a reversal from net water absorption to net secretion and increased mucosal cyclic AMP content by 54%. Additional intra‐arterial infusion of PGE1 resulted in a massive increase in net water secretion and an increase in mucosal cyclic AMP content by about 200%.
Pretreatment with morphine (10 mg/kg, s.c.) reduced the effect of PGE1 on net water flux and completely inhibited its effect on the mucosal cyclic AMP content. Naloxone (10 mg/kg, s.c.) abolished both effects of morphine.
A good correlation (r = 0.99) was demonstrated between mucosal cyclic AMP levels and net water flux.
The present results demonstrate that PGE1 stimulates intestinal fluid secretion by increasing mucosal cyclic AMP levels. The antidiarrhoeal effect of morphine can be explained by its inhibition of the PGE‐mediated increase in cyclic AMP levels, which, in turn, leads to a reduction in intestinal secretion.
CONTRACTILE AND RELAXANT ACTIONS OF PROSTAGLANDINS ON GUINEA‐PIG ISOLATED TRACHEA
Authors: COLEMAN R.A. , KENNEDY I. 
Published: July 2012

The effects of 12 prostaglandins on guinea‐pig isolated trachea have been examined in the presence of indomethacin. Two series of experiments were carried out, the first on preparations without tone (‘zero tone’), and the second on preparations with tone induced with acetylcholine (‘high tone’).
The compounds tested fell into two groups. The first, comprising prostaglandins F1α, F2α F2α acetal, I2 and Wy 17186, contracted both zero and high tone preparations. The second, comprising prostaglandins A1, A2, B1, B2, E1 E2 and F2β, contracted zero, but relaxed high tone preparations. Responses to the second group of compounds are probably the resultant of their contractile and relaxant actions.
The order of potency for contracting zero tone preparations was prostaglandin E (PGE) > F = I = Wy 17186 > B > A, 2‐series compounds being 5 to 18 times more potent than 1‐series compounds.
The order of potency for relaxing high tone preparations was PGE > Fβ > B > A > Wy 17186 > Fα = I = 0. There was little difference between the potency of 1‐ and 2‐series compounds.
The possible relevance of these results to the interpretation of the effects of prostaglandins on human airways is discussed.
ANTAGONISM OF OPIATE MYDRIASIS IN MICE
Authors: KORCZYN AMOS D. , ROCK MEIR 
Published: July 2012

Morphine‐induced mydriasis in mice is antagonized by nalorphine, levallorphan and naloxone in a dose‐dependent manner.
The relative potency of the three agents is 10: 56: 134 respectively, thus being in accordance with other tests of narcotic antagonism. Naloxone has the shortest duration of action.
When injected into naive animals, nalorphine (but not levallorphan or naloxone) produces a slight mydriasis.
Measurement of the diameter of the pupil in mice seems to be a precise, simple and rapid test for studying narcotic antagonist as well as agonist action and has several advantages over standard methods used for this purpose.
COCAINE CUE IN PIGEONS: TIME COURSE STUDIES AND GENERALIZATION TO STRUCTURALLY RELATED COMPOUNDS (NORCOCAINE, WIN 35,428 AND 35,065‐2) AND (+)‐AMPHETAMINE
Authors: JÄRBE TORBJÖRN U.C. 
Published: July 2012

Pigeons trained to discriminate between the presence or absence of effects induced by cocaine hydrochloride (5.6mg/kg) were tested for generalization with norcocaine and two phenyltropane analogues (WIN 35,428 and WIN 35,065‐2). Separate dose‐effect curves were obtained at different intervals after the injections so that possible changes both in potency and duration of action could be evaluated.
Results showed that all of these drugs fully generalized to cocaine. The order of potency was WIN 35,428 > norcocaine > WIN 35,065‐2 > cocaine when tested either at 15 or 60 min after injection. The cocaine‐like effects were strongest for all drugs when tested 15 min after injection as compared to the tests at the 60 min interval. The decay of the cocaine‐like stimulus effects occurred at about the same rate.
Apomorphine (0.3, 0.56 and 1 mg/kg), morphine (3 and 5.6mg/kg), Δ9‐tetrahydrocannabinôl (0.3 and 0.56 mg/kg), and lysergic acid diethylamide (LSD‐25, 0.056 and 0.1 mg/kg) did not induce more than 30% cocaine appropriate responses. (+)‐Amphetamine produced 73% and 85% cocaine appropriate responses depending on the injection‐test interval used, 15 and 30 min respectively.
The amphetamine homologue, para‐hydroxyamphetamine (3.8 mg/kg) did not generalize to cocaine. Tests with 30 mg/kg of procaine produced 40% cocaine appropriate responses. Cocaine is effective also when administered by gavage into the opening of the proventriculus.
The use of the drug discrimination technique for studying structure activity relationships of drugs is discussed.
PHARMACOLOGICAL CHARACTERIZATION OF OPIATE PHYSICAL DEPENDENCE IN THE ISOLATED ILEUM OF THE GUINEA‐PIG
Authors: LUJÀN MIGUEL , RODRIGUEZ RODOLFO 
Published: July 2012

Physical dependence was produced in ilea from naive guinea‐pigs by exposure of the tissues to different opiates for logarithmically‐spaced periods of time (20–320 min). The responsiveness of the tissue to naloxone, as indicated by a strong contracture of the ileum, was enhanced in contrast to that found in intestines not exposed to opiates.
The dose‐response curves to naloxone obtained in tissues individually exposed to different opiates showed that their relative potency in increasing sensitivity to naloxone was as follows: levorphan > morphine > Met‐enkephalin > nalorphine > pentazocine.
The naloxone‐induced response was dose‐dependent and was directly related to the opiate concentration and length of exposure.
Dextrorphan, the inactive isomer of levorphan, did not increase the responsiveness of the tissues to the narcotic antagonist, indicating that the phenomenon is stereospecific.
The naloxone‐induced contraction in ilea exposed for 320 min to morphine (1 × 10−6 m) was not prevented or suppressed by the administration of a large dose of morphine (1 × 10 −5 m) before or immediately after the naloxone challenge.
The evidence presented here shows that a phenomenon resembling in vivo opiate physical dependence can be acutely produced in vitro with pharmacological characteristics similar to other naloxone‐induced abstinence effects.