bluuebunny/crossref_metadata_2025_split huggingface dataset:
CONTRIBUTION OF PROSTAGLANDINS TO THE ADENOSINE TRIPHOSPHATE‐INDUCED CONTRACTION OF RABBIT URINARY BLADDER
Authors: ANDERSSON K.‐E. , HUSTED S. , SJÖGREN C. 
Published: July 2012

Adenosine 5′‐triphosphate (ATP) produced an inital rapid, phasic contraction and a later, slowly developing tonic contraction in the isolated detrusor of the rabbit but mainly a rapid, phasic response in the guinea‐pig bladder.
Electrical field stimulation elicited only a rapid, phasic contraction in both rabbit and guinea‐pig bladders.
Prostaglandin synthesis inhibition by means of indomethacin and suprofen abolished the tonic response to ATP in the rabbit detrusor, leaving the phasic part of the contraction almost unaffected. The ATP‐induced contraction in guinea‐pig bladder was not influenced by indomethacin.
The contractile response of rabbit urinary bladder to prostaglandins F2α and E2 and to carbachol were not significantly influenced by indomethacin. The contractions induced by the prostaglandins were similar to the tonic response to ATP.
Tetrodotoxin, atropine, phentolamine, and theophylline did not alter the ATP‐induced contraction. However, the calcium antagonists, nifedipine and nimodipine, abolished the phasic ATP response and greatly reduced the tonic part of the contraction.
Tachyphylaxis occurred on repeated addition of ATP; the response to field stimulation was progressively reduced only after indomethacin pretreatment.
ATP and prostaglandins may contribute to the non‐adrenergic, non‐cholinergic component of the excitation of rabbit and guinea‐pig bladder.
THERMOREGULATORY EFFECTS OF N6‐2′‐O‐DIBUTYRYL ADENOSINE 3′,5′‐MONOPHOSPHATE IN THE RESTRAINED MOUSE
Authors: DASCOMBE M.J. , MILTON A.S. , NYEMITEI‐ADDO I. , PERTWEE R.G. 
Published: July 2012

The N6‐2′‐O‐dibutyryl derivative of adenosine 3′,5′‐monophosphate (db cyclic AMP) has been micro‐injected into the third cerebral ventricle of the unanaesthetized, restrained mouse and the effects on body temperature and thermoregulatory activities observed.
Db cyclic AMP (4, 16 and 32 μg) injected intracerebroventricularly produced hypothermia when compared with temperature responses to sodium n‐butyrate (6.8 μg).
Hypothermia induced by db cyclic AMP in mice was associated with a fall in oxygen consumption together with behavioural and autonomic heat loss activities but not cutaneous vasodilatation. The effects on rectal temperature and oxygen consumption were dose‐dependent.
The falls in rectal temperature and oxygen consumption induced by db cyclic AMP (4 μg) were decreased by elevation of the environmental temperature from 22 to 32°C and abolished at 36°C.
It is concluded db cyclic AMP may inhibit central events mediating the rise in metabolic heat production in mice upon exposure to cold environments.
THE EFFECTS OF (+)‐ AND (–)‐PROPRANOLOL ON 3H‐TRANSMITTER EFFLUX IN GUINEA‐PIG ATRIA AND THE PRESYNAPTIC β‐ADRENOCEPTOR HYPOTHESIS
Authors: KALSNER STANLEY 
Published: July 2012

The effects of isoprenaline and of the (+)‐ and (–)‐isomers of propranolol on the stimulation‐induced overflow of 3H‐transmitter was assessed in guinea‐pig atria to evaluate the hypothesis of presynaptic β‐adrenoceptors.
Isoprenaline (1.2 × 10−8 m) enhanced the efflux of tritium at 2 and 5 Hz with 100 pulses and did so to a similar extent at both frequencies.
The (–)‐isomer of propranolol (1.0 × 10−7 m) blocked the enhancing effect of isoprenaline but did not by itself modify transmitter efflux.
The (+)‐isomer of propranolol, almost devoid of β‐adrenoceptor blocking properties, was also effective at 1.0 × 10−7 m in blocking the enhancement of tritium efflux by isoprenaline.
The (–)‐isomer of propranolol (1.0 × 10−7 m) blocked almost entirely the inotropic response to isoprenaline (3 × 10−7 m) but even 3.0 × 10−6 m (+)‐propranolol was inneffective in antagonizing the β‐adrenoceptor‐mediated contractile responses to the catecholamine.
It is concluded that the presynaptic site of isoprenaline action does not show the requisite stereospecifity of β‐adrenoceptors and that a ‘non‐specific’ action of the antagonist probably accounts for its reduction of the effect of isoprenaline.
MORPHINE DEPENDENCE AND DOPAMINERGIC ACTIVITY: TESTS OF CIRCLING RESPONSES IN RATS WITH UNILATERAL NIGRAL LESIONS
Authors: HALLIWELL J.V. , KUMAR R. 
Published: July 2012

Rats with unilateral electrolytic lesions involving both parts of the substantia nigra show dose‐related, ipsilateral circling responses to apomorphine which are stable over time.
In non‐tolerant rats, morphine (up to 10 mg/kg) does not elicit any circling behaviour but as tolerance develops to morphine, initially 10 mg/kg daily and then 100 mg/kg daily for about 4 months, the rats show a progressive tendency to walk more towards the side of the lesion. This behaviour is qualitatively different from apomorphine‐induced circling.
When apomorphine (0 to 1.0 mg/kg) and morphine (10 or 100 mg/kg) are tested together, the total amounts of ‘circling’ are increased in an additive manner. However, after 22 h withdrawal from morphine there is a more marked increase in apomorphine‐induced circling which is related to the level of dependence.
It is suggested that the sensitivity of striatal dopamine receptors is not altered by morphine dependence and that the increased response to apomorphine in abstinence probably reflects changes in the modulating actions of other neurotransmitter systems in the striatum.
DECREASE OF SUBSTANCE P IN PRIMARY AFFERENT NEURONES AND IMPAIRMENT OF NEUROGENIC PLASMA EXTRAVASATION BY CAPSAICIN
Authors: GAMSE R. , HOLZER P. , LEMBECK F. 
Published: July 2012

Rats were pretreated with capsaicin (50 mg/kg, s.c.) on the 2nd, 10th, or 20th day of life. Three months later immunoreactive substance P (I‐SP) was determined in skin, sensory nerves and the central nervous system. Neurogenic plasma extravasation was also examined.
Pretreatment at the age of 2 or 10 days resulted in a decrease (26 to 69%) of I‐SP in skin, saphenous and vagus nerve, dorsal roots, dorsal half of the spinal cord, and medulla oblongata. The I‐SP content of the ventral half of the spinal cord, of midbrain, hypothalamus, striatum, cortex, and cerebellum remained unchanged. Neurogenic plasma extravasation was inhibited by more than 80%.
In contrast to this irreversible effect of capsaicin on newborn rats, pretreatment of 20 day old rats led to reversible depletion of I‐SP and to reversible impairment of neurogenic plasma extravasation.
Capsaicin pretreatment of adult rats caused a marked depletion of I‐SP in the skin of the hind paw and an impairment of neurogenic plasma extravasation. A similar decrease of I‐SP was seen after chronic denervation of the skin.
Intra‐arterial infusion of substance P (threshold dose 5 × 10−13mol/min) or physalaemin induced dose‐dependent plasma extravasation. Somatostatin, vasoactive intestinal polypeptide, caerulein and the enkephalin‐analogue FK 33–824 were ineffective in doses 100 fold higher.
The results indicate that the action of capsaicin on substance P neurones is restricted to primary sensory neurones. Since in every case a decreased substance P content of the skin was associated with impaired neurogenic plasma extravasation, it is suggested that release of substance P is involved in neurogenic plasma extravasation.
A CALCIUM‐DEPENDENT ACETYLCHOLINE DEPOLARIZATION BLOCKED BY METHOXYVERAPAMIL (D600) AND PROCAINE IN SNAIL NEURONES
Authors: ISRAEL JEAN‐MARC , MEUNIER JEAN‐MARIE 
Published: July 2012

Repetitive application of acetylcholine (ACh) revealed two types of ACh depolarization in two types of snail neurone, depending on their desensitization properties.
Further experiments were carried out on neurones which displayed a rapidly desensitizing response.
The amplitude of the response depended on the external sodium and calcium levels.
Procaine antagonized ACh effects with the same efficiency as atropine or hexamethonium, half maximal depression being obtained at a concentration of 10−4m. The blocking effect was independent of the dose of ACh.
The depression of the ACh‐induced depolarization by cobalt ions and D600 suggests that calcium may participate in this response.
EFFECTS OF HYDRALAZINE AND VERAPAMIL ON PHOSPHORYLASE ACTIVITY AND GUANOSINE CYCLIC 3′,5′‐MONOPHOSPHATE LEVELS IN GUINEA‐PIG TAENIA COLI
Authors: DIAMOND JACK , JANIS RONALD A. 
Published: July 2012

The roles of guanosine cyclic 3′,5′‐monophosphate (cyclic GMP) and calcium in the relaxation produced by hydralazine and verapamil in potassium‐depolarized guinea‐pig taenia coli have been investigated.
Depolarization of isolated strips of guinea‐pig taenia coli by 124 mm KCl caused sustained contractures and increases in tissue levels of cyclic GMP.
The KCl‐induced increases in cyclic GMP levels appeared to be calcium dependent. No increases in cyclic GMP levels were seen in strips of taenia coli depolarized in the absence of calcium. Re‐addition of calcium to the depolarizing solution contracted the muscles and increased cyclic GMP levels. When calcium was removed from the depolarizing solution during the sustained, tonic phase of a KCl‐induced contracture, both tension and cyclic GMP levels returned to control values.
Administration of 50 um verapamil to KCl‐contracted muscles completely relaxed the muscles and caused cyclic GMP levels to return to control values within 14 min. Hydralazine, 2 mm, on the other hand, relaxed the depolarized muscles without lowering cyclic GMP levels. No significant changes in cyclic AMP levels were seen in any of these experiments.
Similar results were obtained in an analogous series of experiments in which glycogen phosphorylase activity was measured instead of cyclic GMP levels. Activation of phosphorylase during contractions of guinea‐pig taenia coli had previously been reported to be a calcium‐dependent phenomenon.
It was concluded that increases in tissue levels of cyclic GMP (or of cyclic AMP) were not responsible for the relaxant effects of hydralazine or verapamil in these experiments. It was also suggested, based on our results, that verapamil exerted its relaxant effects in the depolarized taenia coli by lowering cytoplasmic calcium levels, whereas hydralazine relaxed the depolarized muscles without lowering intracellular calcium activity.
PRELIMINARY PHARMACOLOGICAL CHARACTERIZATION OF THE BOVINE ISOLATED BRONCHIAL ARTERY STRIP: A NEW PREPARATION
Authors: AROWOLO R.O.A. , EYRE P. 
Published: July 2012

This paper describes a preliminary pharmacological study of the isolated helical strip of bovine bronchial artery under isotonic conditions in Krebs‐Henseleit solution.
The tissue contracted to histamine and 5‐hydroxytryptamine (5‐HT), actions which were selectively antagonized by mepyramine and methysergide respectively. Histamine was not inhibited by metiamide and 5‐HT was not affected by morphine.
Slow reacting substance of anaphylaxis (SRS‐A), prostaglandin F2α (PGF2α) and PGE2 were spasmogenic, whereas PGE1 caused relaxation. No potential antagonists of these agents were tested.
Carbachol, at all concentrations, caused contractions of the bronchial artery which were completely, irreversibly blocked by atropine.
The spasmogenic action of phenylephrine was selectively blocked by dibenamine. Vessel strips which were partially contracted to histamine, relaxed to isoprenaline and salbutamol. The action of isoprenaline was inhibited similarly by either propranolol or practolol. The evidence therefore suggests the presence of functional α, β1 and β2‐adrenoceptors.
RELEASE‐MODULATING ACETYLCHOLINE RECEPTORS ON CHOLINERGIC NEURONES OF THE GUINEA‐PIG ILEUM
Authors: FOSBRAEY P. , JOHNSON E.S. 
Published: July 2012

Twitch responses of the guinea‐pig ileum to electrical transmural stimulation (0.2 Hz) were smaller after a dose of acetylcholine (ACh) than before it. The magnitude of the post‐ACh inhibition of twitch was dose‐dependent.
The post‐ACh inhibition of twitch could not be explained in terms of post‐junctional desensitization and was not modified by guanethidine, thymoxamine, propranolol or naloxone. Inhibition of twitch also followed high frequency stimulation (10 Hz) but this inhibition, unlike that following ACh, was partially antagonized by naloxone.
Hexamethonium (C6) in concentrations known to block contractions to nicotine, potentiated the post‐ACh inhibition of twitch and modified the pattern of recovery. An initial rapid phase followed by a slower phase was converted by C6 to an initial slow phase followed by a more rapid rate of recovery.
The C6‐sensitive (nicotinic) component of twitch recovery after ACh was also dose‐dependent and contributed greatly to the rapid recovery during the first minute after ACh washout, whereas during the same period the C6‐resistant inhibition remained relatively constant; thereafter both components declined. The C6‐resistant inhibition was considered to be due to the activation of prejunctional muscarinic receptors.
5‐Hydroxytryptamine (5‐HT) and nicotine also caused inhibition of twitch but the pattern of response differed from those due to ACh, the maximum inhibition usually being produced 1 min after recommencing stimulation. High doses of 5‐HT produced inhibitory responses similar to those following ACh, whereas nicotine produced a characteristic triphasic pattern of response.
It is concluded that ACh acts on at least two prejunctional receptors subserving a modulatory role on transmitter release, a nicotinic receptor whose activation enhances ACh output and a muscarinic receptor whose activation leads to an inhibition of transmitter secretion.
THE EFFECTS OF AROMATIC AMINO ACID DERIVATIVES ON THE EXCITABILITY OF AN IDENTIFIABLE GIANT NEURONE OF THE AFRICAN GIANT SNAIL (Achatina fulica Férussac)
Authors: TAKEUCHI HIROSHI , TAMURA HIROKO 
Published: July 2012

The effects of derivatives of aromatic amino acids on the excitability of an identifiable giant neurone (TAN, tonically autoactive neurone) of the African giant snail (Achatina fulica Férussac) were examined.
The following substances had marked inhibitory effects on TAN using bath application: N‐β‐phenylpropionyl‐l‐Tyr and N‐β‐phenylpropionyl‐l‐Trp (critical concentration, 3 × 10−7 m), N‐β‐phenylpropionyl‐l‐Phe, N‐cinnamoyl‐dl‐Trp and N‐phenoxyacetyl‐l‐Trp (critical concentration, 10−5 to 3 × 10−5 m). However, N‐β‐phenylpropionyl‐d‐Tyr and N‐β‐phenylpropionyl tyramine had no effect.
Microdrop (150 μm in diameter) application of a solution of N‐β‐phenylpropionyl‐l‐Tyr or N‐β‐phenylpropionyl‐l‐Trp containing about 100 pg resulted in marked inhibitory effects on TAN. The effect was observed in Ca2+‐free, Mg2+‐rich (24 mm) solution. Substitution of Cl− by acetate did not alter the response. This indicates that the two substances act directly on the TAN membrane and not via synaptic influences, and that the inhibition produced by the two substances is not due to the permeability increase of the TAN membrane to Cl−.
THE EFFECTS OF CASTRATION ON NEUROTRANSMISSION IN THE RAT VAS DEFERENS
Authors: MACDONALD A. , MCGRATH J.C. 
Published: July 2012

Responses to adrenoceptor agonist drugs and to field stimulation were examined in vasa deferentia from adult castrated or intact rats. Isometric tension was recorded in vitro from whole or transversely bisected vasa.
After castration vasa exhibited spontaneous contraction, noradrenaline no longer produced a ‘tonic’ contraction but increased the ‘phasic’ spontaneous activity and salbutamol inhibited spontaneous activity by a β‐adrenoceptor‐mediated mechanism.
After castration the ‘adrenergic’ components of the contractile responses to field stimulation were lost whereas ‘noradrenergic’ responses remained, pre‐junctional inhibition of field stimulation‐induced contractions by either endogenous or exogenous activation was lost but adrenergic terminals could still be demonstrated microscopically.
Testosterone treatment partially reversed these effects of castration.
The relevance of these results to the nature of neurotransmission and to the genesis of spontaneous contraction in the vas deferens is discussed.
BEHAVIOURAL CHANGES INDUCED BY N,N‐DIMETHYLTRYPTAMINE IN RODENTS
Authors: JENNER P. , MARSDEN C.D. , THANKI C.M. 
Published: July 2012

N,N‐Dimethyltryptamine (DMT) in pargyline pretreated rodents induced a dose‐dependent behavioural syndrome consisting of hyperactivity, prostration and hindlimb abduction, mild tremor, Straub tail, retropulsion and jerking.
In rats pretreated with pargyline, the behavioural syndrome induced by DMT differed from that induced by l‐tryptophan or quipazine, in the lack of forepaw treading and head‐weaving and in the presence of only mild tremor.
The hyperactivity component of the DMT‐induced behavioural syndrome in pargyline‐pretreated mice was potentiated by cyproheptadine, methergoline, and mianserin, inhibited by cinanserin, haloperidol, pimozide, methiothepin and propranolol, and not affected by 501C67‐sulphate and methysergide.
The maximal behavioural changes induced by DMT in rats, other than hyperactivity, were unaffected by pretreatment with cyproheptadine, methysergide, and cinanserin. However, propranolol reduced the intensity of all behavioural effects apart from body jerking, and methergoline decreased the duration of prostration. Phenoxybenzamine and haloperidol, in contrast, enhanced prostration.
DMT plus pargyline did not induce circling behaviour in mice with a unilateral 6‐hydroxydopamine lesion of the nigro‐striatal pathway.
The DMT‐induced behavioural syndrome appears to consist of two components, (a) hyperactivity and (b) other behavioural changes. They differ in their response to drugs affecting brain monoamines. The hyperactivity component may be expressed via dopamine mechanisms, but the other behavioural changes are not. The two behaviours do not respond consistently to drugs believed to alter brain 5‐hydroxytryptamine function.
LACK OF CORRELATION BETWEEN PRESYNAPTIC INHIBITION OF NORADRENALINE RELEASE AND END ORGAN RESPONSES DURING NERVE STIMULATION
Authors: DUBOCOVICH MARGARITA L. , LANGER S.Z. , MASSINGHAM R. 
Published: July 2012

LD 3098 (cirazoline) is an imidazoline derivative, possessing agonist properties at α‐adrenoceptor sites.
When transmitter release was measured directly as tritium overflow from perfused cat spleen preparations, prelabelled with [3H]‐noradrenaline, LD 3098 was found to be 10 times more selective for presynaptic than for postsynaptic α‐adrenoceptors.
In addition, in this preparation, LD 3098 appears to induce a postsynaptic sensitization to the transmitter released by nerve depolarization because under conditions in which [3H]‐noradrenaline overflow decreased, there was a paradoxical potentiation in the response to nerve stimulation. This potentiation also occurred with a concentration of LD 3098 that did not per se affect stimulation‐evoked [3H]‐noradrenaline release or the basal perfusion pressure of the spleen.
Both the reduction in 3H‐transmitter release induced through activation of α‐presynaptic adrenoceptors and the potentiation of the responses to nerve stimulation were concentration‐dependent phenomena.
In pentobarbitone anaesthetized dogs, the heart rate response to low frequency ansa‐subclavia stimulation was not affected by LD 3098. Whilst the α1 mediated increase in blood pressure responses to injected noradrenaline and tyramine was significantly potentiated by LD 3098, the β1‐mediated heart rate responses to these injected amines were not modified in the presence of LD 3098.
Thus it is possible that the failure to detect any presynaptic effects with LD 3098 when transmitter release is measured indirectly at the level of the postsynaptic responses is due to end organ sensitivity changes.
These findings emphasize that caution is necessary when assessing presynaptic α‐adrenoceptor effects through end organ responses to nerve stimulation both in vitro and in vivo and the need for measurements of transmitter overflow as well as adequate postsynaptic controls in such experiments.
COMPARISON OF DESENSITIZATION AND TIME‐DEPENDENT BLOCK OF THE ACETYLCHOLINE RECEPTOR RESPONSES BY CHLORPROMAZINE, CYTOCHALASIN B, TRITON X‐100 AND OTHER AGENTS
Authors: ANWYL ROGER , NARAHASHI TOSHIO 
Published: July 2012

Chlorpromazine, cytocholasin B, Triton X‐100, lidocaine, QX‐314, pentobarbitone, heptanol and ethanol, but not benzocaine or methylguanidine, caused a time‐dependent inhibition of acetylcholine (ACh) potentials. Increasing the concentration of the agents increased the rate of inhibition.
The recovery rate from the time‐dependent inhibition was the same as from desensitization except in Triton X‐100 which slowed the recovery.
Hyperpolarizing the membrane potential caused an increase in the rate of the time‐dependent inhibition.
It is suggested that the time‐dependent inhibition and desensitization are very similar phenomena, with either ACh (in desensitization) or an agent (in time‐dependent inhibition) causing a block of the activated ACh receptor, and with dissociation from the binding site being very slow.
Many of the agents also cause a steady state inhibition of the ACh receptor which appears to be caused by a separate blocking action of the agents.
BLOCKADE OF STRIATAL NEURONE RESPONSES TO MORPHINE BY AMINOPHYLLINE: EVIDENCE FOR ADENOSINE MEDIATION OF OPIATE ACTION
Authors: PERKINS MARTIN N. , STONE TREVOR W. 
Published: July 2012

The responses of cortical and striatal neurones to morphine and adenosine applied iontophbretically have been studied in the male rat.
The majority of cells (57%) within the corpus striatum were profoundly inhibited, and a smaller proportion (18%) excited by morphine. Adenosine depressed the firing rate of 30/44 cells in the striatum, excitation never being observed. In contrast, the responses of cortical cells to morphine were typically weak and required longer ejection pulses to effect comparable changes in firing rate.
Aminophylline applied iontophoretically, as an anion, proved able to antagonize reversibly both morphine and adenosine in parallel.
On a number of cells, γ‐aminobutyric acid (GABA) was used as a control depressant but aminophylline did not appear to reduce these responses.
The responses to morphine (both inhibitory and excitatory) were not easily antagonized by naloxone. Typically, excitatory responses were easier to antagonize than the inhibitory ones.
It is concluded that a consequence of the interaction of morphine with its receptors may be the release of adenosine which subsequently produces the inhibition observed with morphine.
DIABETOGENIC EFFECTS OF CHRONIC ORAL CADMIUM ADMINISTRATION TO NEONATAL RATS
Authors: MERALI Z. , SINGHAL R.L. 
Published: July 2012

Chronic exposure of neonatal rats to oral cadmium (Cd) (0.1 and 1.0 μg/g daily for 45 days) disturbed glucose homeostasis, as reflected by hyperglycaemia, reduced liver glycogen and enhanced gluconeogenic potential of hepatic tissue.
This Cd‐exposure regimen also increased hepatic cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) which was accompanied by enhancement of basal, adrenaline and glucagon‐stimulated form(s) of adenylate cyclase.
In order to assess the responsiveness of pancreatic beta cells to glucose, islets isolated from control as well as Cd‐exposed animals were incubated in vitro and their rate of insulin secretion determined. In the presence of glucose 0.5 mg/ml, there was no significant difference in the rate of insulin release. However, at higher glucose concentrations (1.5 and 3.0 mg/ml), the islets from Cd‐exposed rats released significantly less insulin than those of control animals.
The results are discussed in relation to the possible mechanism of the diabetogenic effect of Cd.