bluuebunny/crossref_metadata_2025_split huggingface dataset:
DIFFERENT HYPOTHALAMIC RECEPTORS MEDIATE 5‐HYDROXYTRYPTAMINE‐ AND TRYPTAMINE‐INDUCED CORE TEMPERATURE CHANGES IN THE RAT
Authors: COX B. , LEE T.F. , MARTIN D. 
Published: July 2012

Unilateral intrahypothalamic injection of 5‐hydroxytryptamine (5‐HT) caused a dose‐related fall in core temperature in rats, whereas injection of tryptamine into the same site caused a dose‐related rise in core temperature.
The core temperature changes induced by 5‐HT or tryptamine were inhibited by intrahypothalamic pretreatment with indoleamine receptor antagonists in a dose‐related manner.
Other neurotransmitter antagonists, haloperidol, atropine, phentolamine and (—)‐propranolol, had no significant effect on core temperature changes induced by 5‐HT or tryptamine.
A differential antagonism was observed for the indoleamine receptor antagonists against 5‐HT and tryptamine‐induced core temperature changes. Methergoline and triflupromazine were more selective against tryptamine‐induced hyperthermia, while cyproheptadine was more selective against 5‐HT‐induced hypothermia.
Intrahypothalamic pretreatment with 5,7‐dihydroxytryptamine (5,7‐DHT) 42 nmol in 2 μl inhibited tryptamine‐induced hyperthermia, but was without effect on 5‐HT‐induced hypothermia.
These results suggest the possible existence of two different receptor populations within the preoptic anterior hypothalamus in rats; one specific for 5‐HT and the other for tryptamine.
THE EFFECTS OF ATENOLOL ON SPONTANEOUS AND REFLEX ACTIVITY OF THE SYMPATHETIC NERVES IN THE ANAESTHETIZED CAT
Authors: EVELYN M.SCOTT 
Published: July 2012

The reduction in the sympathetic efferent discharge observed after propranolol may be due to either a central or a peripheral effect. The β‐adrenoceptor blocking drug, atenolol, is not thought to enter the brain and therefore any reduction in the level of sympathetic efferent discharge observed after atenolol is likely to be mediated peripherally rather than centrally.
Cats were anaesthetized with α‐chloralose and artificially ventilated and a number of variables known to affect the sympathetic nerves were monitored throughout the experiment and maintained within normal limits. Recordings were made from few fibre preparations from the lumbar trunk and the renal nerves. Blood pressure was either raised or lowered by the injection of phenylephrine (1–4 μg/kg) or glyceryl trinitrate (2–20 μg/kg) and the sympathetic efferent discharge was recorded over a range of blood pressures when the blood pressure was steady.
Thirty min after giving atenolol (3 mg/kg) the blood pressure, heart rate and sympathetic efferent discharge were significantly reduced. Atenolol also attenuated the reflex responses of the sympathetic nerves to changes in the blood pressure.
It is suggested that atenolol has its actions on sympathetic nerves at a site outside the CNS and some possible mechanisms are discussed.
EVIDENCE IN SUPPORT OF THE P1/P2 PURINOCEPTOR HYPOTHESIS IN THE GUINEA‐PIG TAENIA COLI
Authors: BROWN CHRISTINE M. , BURNSTOCK G. 
Published: July 2012

The relaxations induced by adenosine 5′‐triphosphate (ATP), adenosine 5′‐diphosphate (ADP), adenosine 5′‐monophosphate (AMP) and adenosine on the carbachol‐contracted taenia coli of the guinea‐pig have been studied. ATP and ADP produce similar responses which differ in nature and time course from those of AMP and adenosine.
Theophylline, at concentrations (25–200μm) lower than those which produce significant phosphodiesterase inhibition, blocks the effects of AMP and adenosine but fails to antagonize the responses elicited by ATP and ADP. The antagonism of adenosine by theophylline appears to be competitive.
Apamin (1–100 nM) blocks the inhibitory effects of ATP and ADP but fails to antagonize the responses to AMP and adenosine. The antagonism by apamin is non‐competitive.
The results indicate that ATP and adenosine relax the taenia coli by activating different receptors and are consistent with the P1 P2 purinoceptor hypothesis.
INHIBITION OF PROSTAGLANDIN E1‐RESPONSIVE PLATELET ADENYLATE CYCLASE BY HEPARIN: A STUDY OF THE MECHANISM OF INHIBITION AND ITS RELEVANCE TO PLATELET AGGREGATION
Authors: AMIRRASOOLI H. , NEIL S. MAC , TOMLINSON S. 
Published: July 2012

Heparin can produce platelet aggregation in vitro and in vivo; it has been proposed that this may be due to the reported inhibition of the prostaglandin E1 (PGE1)‐stimulated adenylate cyclase of the platelet by heparin.
The effect of heparin on the cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) response to PGE1 was measured in intact and broken platelets both in vitro and in platelets obtained from normal subjects during intravenous infusion with herapin.
In platelet lysates, heparin produced a dose‐related inhibition of PGE1‐stimulated adenylate cyclase. The maximum response to PGE1 was reduced, with half‐maximal inhibition occurring at
μg/ml heparin. This inhibition could be prevented by protamine sulphate.
Heparin did not affect PGE1‐stimulated cyclic AMP production in intact platelets either in vitro or in platelets taken during the infusion of 5,000 iu heparin over 2h to 2 normal volunteers. Similarly, preincubation of platelets with heparin for up to 3 h at 37°C did not affect platelet adenylate cyclase.
The effects of heparin were very similar to those of fluoride on the platelet adenylate cyclase: heparin and fluoride increased basal enzyme activity slightly (3–4 fold) but their effects were not additive; both inhibited the response to PGE1 by approximately 50% when added directly to the assay and the inhibitory effects of the two were not additive; preincubation of membranes with either heparin or fluoride produced an irreversible state of inhibition.
As heparin inhibits PGE2‐stimulated adenylate cyclase activity only in broken platelets, we suggest that the aggregatory effects of heparin are probably independent of any action on cyclic AMP production.
TRAPPED BLOOD ELEMENTS WITHIN THE DECIDUA OF THE RAT PREGNANT UTERUS GENERATE A LIPOXYGENASE PRODUCT(S) WHICH INHIBITS MYOMETRIAL PROSTACYCLIN SYNTHESIS
Authors: TAHIR K.E.H. EL , WILLIAMS K.I. 
Published: July 2012

Prostacyclin (PGI2) production by chopped segments of rat pregnant uterus was low compared with synthesis by separated myometrial tissue. Incubation of separated myometrium with decidua (2:1 by weight) led to an inhibition of myometrial PGI2 output.
Boiling decidual tissue abolished the inhibitory influence on myometrial PGI2 output. Preincubation of decidua with 5, 8, 11, 14‐eicosatetraynoic acid (ETA) (30 m̀g/ml) also suppressed decidual inhibitory activity but indomethacin (30 m̀g/ml) was ineffective.
Incubation of decidual and myometrial tissue with arachidonic acid (AA) 10m̀g/ml did not increase the inhibition of myometrial PGI2 synthesis, even if the decidua were pre‐incubated with indomethacin.
Myometrial PGI2 production was reduced if the chopped tissue was pre‐incubated with soya bean lipoxidase for 10 min at 4°C. This reduction was reversed if the lipoxidase was incubated with ETA (30°g/ml) for 30 min at 37°C before addition to the myometrial tissue.
Perfusion of the uterus to remove blood elements removed the inhibitory action that the decidua exerted upon myometrial PGI2 production. PGI2 synthesis by separated decidual and whole uterine tissue was markedly elevated.
The addition of rat blood platelets (0.75 × 109/ml) to incubations of perfused decidual tissue reduced PGI2 output and restored the inhibitory action that the decidua exerted on myometrial PGI2 synthesis.
It is concluded that a lipoxygenase enzyme contained in blood platelets trapped within the decidual vasculature produces a hydroperoxy acid which inhibits decidual PGI2 production or myometrial PGI2 synthesis when the tissues are incubated together. It is suggested that perfusion is a pre‐requisite before study of PGI2 synthesis in highly vascularised tissues.
The pathophysiological importance of such platelet lipoxygenase products is discussed.
AN INVESTIGATION INTO THE TYPE OF β‐ADRENOCEPTOR MEDIATING SYMPATHETICALLY ACTIVATED RENIN RELEASE IN THE CAT
Authors: JOHNS EDWARD J. 
Published: July 2012

Stimulation of the renal nerves in the cat was previously shown to cause renin release which could be blocked by propranolol. An attempt was made in this study to determine the type of β‐adrenoceptor mediating this response.
In anaesthetized, unilaterally nephrectomized cats, a comparison was made of the ability of two selective β‐adrenoceptor antagonists to block the tachycardia and hypotension caused by isoprenaline (mediated respectively by β1‐ and β2‐adrenoceptors) and the release of renin caused by renal nerve stimulation.
Isoprenaline (mean dose of 0.224 ±0.022 nmol/kg), increased heart rate by approximately 43 beats/min and decreased mean blood pressure by 47 mmHg. Stimulation of the distal cut ends of the renal nerves, at a rate sufficient to reduce renal blood flow by 30%, resulted in an approximately 150% increase in plasma renin activity.
Administration of the selective β1‐adrenoceptor antagonist, atenolol (0.38 to 11.28μmol/kg), caused a dose‐related inhibition of nerve stimulated renin release and of isoprenaline‐induced tachycardia, with no diminution of the vasodepressor response to isoprenaline; in contrast, the selective β2‐adrenoceptor antagonist, erythro‐DL‐(7‐methylindan‐4‐yloxy)‐3‐isopropylamino‐butan‐2‐ol (ICI 118, 551, 0.03 to 2.86μmol/kg), caused a dose‐related inhibition of the isoprenaline‐induced vasodepression without altering the increase in plasma renin activity caused by renal nerve stimulation. Only at the highest dose of ICI 118, 551 was there a reduction of isoprenaline‐induced tachycardia, by about 40%.
The selective inhibition of neurally activated renin release by atenolol but not by ICI, 118, 551 is consistent with the suggestion that the β‐adrenoceptors mediating renin release resemble those in the heart more closely than those in peripheral blood vessels.
SITE OF ANALGESIC ACTION OF A NON‐STEROIDAL, ANTIINFLAMMATORY DRUG, TOLMETIN SODIUM, IN RATS
Authors: NAKAMURA HIDEO , SHIMIZU MASANAO 
Published: July 2012

The site of the analgesic action of tolmetin sodium was investigated by use of the acetic acid writhing test in rats.
Tolmetin sodium was administered to the rat between 15 and 60 min after an intraperitoneal injection of 1 ml of a 1% acetic acid aqueous solution. Number of writhings was counted for 20 min beginning from 60 min after acetic acid injection.
When the rat was given tolmetin sodium 5 mg/kg orally, a relatively large quantity of tolmetin was found in the peritoneal exudate and there was a rough correlation between anti‐writhing activity and the exudate tolmetin content.
Anti‐writhing ED50 of tolmetin sodium was 1.42 (0.82‐2.91) and 92.0 (57.0–140) μg/kg when given intraperitoneally and intravenously, respectively, and the potency ratio of intraperitoneal to intravenous tolmetin sodium was 40.0 (18.5–80.2). This potency ratio for salicylic acid and morphine hydrochloride was 19.4 and 1.0, respectively.
When equipotent doses (5 fig/kg i.p.; 200 μg/kg i.v.) of tolmetin sodium were administered to the rat, the plasma tolmetin level after the intraperitoneal administration was less than one‐fortieth that after the intravenous administration during the counting time of 20 min, while both the peritoneal exudate contents of tometin were nearly equal.
From these results, it is concluded that the site of anti‐writhing action of tolmetin sodium is in the peritoneum and that tolmetin sodium produces its anti‐writhing action mainly by a peripheral mechanism in the rat.
MECHANISM OF ACTION OF ANGIOTENSIN II ON EXCITATION‐CONTRACTION COUPLING IN THE RAT PORTAL VEIN
Authors: HAMON GILLES , WORCEL MANUEL 
Published: July 2012

The action of angiotensin II (At II) has been studied on the electrical and mechanical activity of the vascular smooth muscle of the rat portal vein.
At low concentrations (between 5 × 10−10 and 10−9m) At II induces an acceleration of spontaneous action potential (AP) discharge without change in the resting membrane potential. The frequency and size of the associated contractions are simultaneously augmented. Under these conditions the size of the spikes is not affected, thus suggesting that At II triggers the release of Ca from internal stores.
The increase in AP discharge rate produced by low concentrations of At II results from an acceleration of the pacemaker potential. Furthermore, in the presence of 10 mm tetraethylammonium (TEA), there is an acceleration of the repolarizing phase of AP.
Ouabain (10−3 m) inhibits the increase in rhythmic activity induced by low concentrations of At II (in the presence of 10 mm TEA), thus suggesting that the Na‐K pump is directly or indirectly involved in this action of the peptide.
At higher concentrations, At II produces a concentration‐dependent depolarization with an EC50 of 1.2 × 10−8m and a maximum of 10−7m. The associated contraction has an EC50 of 3.3 × 10−8 m and a maximum of 3 × 10−7 m.
Ouabain (3 × 10−3 m) depolarizes the cell membrane. Under these conditions, At II (10−7 m) has a slight depolarizing effect, but it still produces a large tonic contraction.7 It is concluded, that At II acts on different steps of excitation‐contraction coupling, depending on the concentration. At low levels, the peptide mainly accelerates spike discharge, through a mechanism involving the Na‐K pump. At higher concentrations, At II depolarizes the cell membrane. The contraction is then activated by the influx of Ca2+ due to secondary AP discharge and the release of Ca2+ from intracellular stores. Pharmacomechanical coupling has an important role in the triggering of contractions both at high and at low concentrations of At II.
POSTSYNAPTIC EFFECTS OF SOME CENTRAL STIMULANTS AT THE NEUROMUSCULAR JUNCTION
Authors: GAGE PETER W. , SAH PANKAJ 
Published: July 2012

Miniature endplate currents (m.e.p.cs) were recorded with extracellular electrodes from sartorius muscles of toads.
Central excitant analogues of amylobarbitone (3M2B) and halothane (DBE) decreased the amplitude and time constant of decay of m.e.p.cs and hence reduced the amplitude of miniature endplate potentials. The decay remained exponential with single time constant.
A central excitant analogue of ether (indoklon) reduced the amplitude of m.e.p.cs and made their decay biphasic. The decay could be fitted by the sum of two exponentials.
Bemegride, a central excitant, prolonged m.e.p.cs. Their decay remained exponential with single time constant. The effect was not due to inhibition of acetylcholinesterase.
All of the drugs tested, including amylobarbitone, reduced the temperature‐sensitivity of the decay of m.e.p.cs.
The biphasic decay of m.e.p.cs caused by indoklon could not be explained simply by supposing that the drug blocked open endplate channels unless it was assumed that the normal rate of channel closing also increased and became much less temperature‐sensitive than normal.
CHANGES IN THE RESPONSE OF GUINEA‐PIG AIRWAYS in vivo AND in vitro TO CIMETIDINE AND PROPRANOLOL DURING DEVELOPMENT
Authors: BRINK CHARLES , DOUGLAS JAMES S. , DUNCAN PAMELA G. 
Published: July 2012

Airway responses were examined in isolated tissues and in whole animal preparations of female albino guinea‐pigs of known age.
Tone induced with acetylcholine in tracheal and bronchial tissues from young and old female guinea‐pigs was not reduced by dimaprit or 4‐methyl histamine even in tissues pretreated with mepyramine maleate.
Antagonism of H2‐receptors with cimetidine did not affect the potency or efficacy of histamine in tracheal tissues from animals of either age group.
After cimetidine treatment the potency of histamine was increased in bronchial tissues from old but not young animals. The sensitizing effect was still demonstrable in tissues incubated with indomethacin.
In vivo airway sensitivity to threshold concentrations of histamine in animals from either age group was unaffected by cimetidine treatment.
Propranolol enhanced airway responses to histamine aerosols in young but not old guinea‐pigs.
Cimetidine was without effect on histamine sensitivity in young guinea‐pigs after propranolol treatment but significantly reduced airway sensitivity to histamine in old guinea‐pigs.
Our data show that (a) H2‐receptors are of no physiological significance for airway responses to histamine in vitro or in vivo and (b) during development the modulating actions of catecholamines upon airway responses are significantly reduced.
DIFFERENTIAL PULSE VOLTAMMETRY IN THE ANAESTHETIZED RAT: IDENTIFICATION OF ASCORBIC ACID, CATECHOL AND INDOLEAMINE OXIDATION PEAKS IN THE STRIATUM AND FRONTAL CORTEX
Authors: BRAZELL M.P. , MARSDEN C.A. 
Published: July 2012

Differential pulse voltammetric scans recorded using graphite paste working electrodes implanted in the striatum and frontal cortex of anaesthetized rats exhibited up to three distinct oxidation peaks at potentials between —0.1 and + 0.5 V.
The first peak at about +0.12 V was selectively increased by the micro‐infusion of ascorbic acid (5 × 10−6m) close to the surface of the working electrode implanted in either the striatum or the frontal cortex.
The second peak at about + 0.22 V was selectively increased by micro‐infusing either dopamine or 3,4‐dihydroxyphenylacetic acid, (5 × 10−6 m).
The third peak at approximately + 0.35 V was selectively increased in a dose‐related manner by the micro‐infusion of either 5‐hydroxytryptamine, (7.5 × 10−6 m to 7.5 × 10−5 m) or 5‐hydroxyindole‐3‐acetic acid, (2.5 × 10−5 m to 6 × 10−4m).
The results show that differential pulse voltammetry can be used to obtain qualitative and quantitative information about catechol and indoleamine neurones in vivo.
MODIFICATION OF THE ANTINOCICEPTIVE EFFECT OF MORPHINE BY CENTRALLY ADMINISTERED DIAZEPAM AND MIDAZOLAM
Authors: MANTEGAZZA PAOLO , PARENTI MARCO , TAMMISO REMIGIO , VITA PAOLO , ZAMBOTTI FERNANDA , ZONTA NERINA 
Published: July 2012

Intracerebroventricular administration of diazepam or midazolam decreased the antinociceptive effect of morphine in rats as measured by the ‘tail flick’ method.
Midazolam, injected into the periaqueductal grey matter (PAG) antagonized the analgesic effect of morphine. The action of midazolam was partially reversed by bicuculline.
These findings support the view that the effect of benzodiazepines on morphine antinociception may be mediated through γ‐aminobutyric acid receptors.
INVOLVEMENT OF 5‐HYDROXYTRYPTAMINE IN THE ANALGESIC ACTION OF PETHIDINE AND MORPHINE IN MICE
Authors: BOTTING REGINA , MORINAN ALUN 
Published: July 2012

Groups of mice were pretreated with the 5‐hydroxytryptamine (5‐HT) depletors, fenfluramine or p‐chlorophenylalanine (PCPA), followed by pethidine or morphine.
Fenfluramine alone produced a short lasting analgesia but PCPA was without any effect.
Pethidine and morphine both increased hot plate reaction times measured after 30 min.
Pre treatment with PCPA attenuated morphine analgesia but did not affect pethidine analgesia. Fenfluramine did not alter the response to either analgesic.
PCPA produced a significant depletion of brain 5‐HT levels which was not reversed by the analgesics. The fenfluramine‐induced decrease in 5‐HT was reversed by morphine but not by pethidine.
The results support the involvement of 5‐HT in the antinociceptive action of morphine in the mouse.
PROSTAGLANDIN ENDOPEROXIDES, THROMBOXANE A2 AND ADENOSINE DIPHOSPHATE IN COLLAGEN‐INDUCED AGGREGATION OF RABBIT PLATELETS
Authors: LEWIS G. P. , WATTS I. S. 
Published: July 2012

A bioassay technique is described for simultaneously monitoring rabbit platelet aggregation with measurement of thromboxane A2 (TXA2) and prostaglandins released in response to collagen or arachidonic acid (AA).
Five imidazole derivatives were examined as inhibitors of thromboxane synthetase and compared with the effect of the cyclo‐oxygenase inhibitor indomethacin; 1‐(7‐carboxyheptyl) imidazole was identified as the most potent and selective inhibitor of thromboxane synthetase and was used with indomethacin to investigate the relative contribution of the prostaglandin endoperoxides prostaglandin G2 (PGG2)/PGH2 and TxA2 in mediating platelet aggregation induced by collagen or AA.
Platelet aggregation induced by a low concentration of collagen was abolished by indomethacin and carboxyheptylimidazole whilst in response to a high concentration or collagen only partial inhibition of aggregation occurred.
The contribution of adenosine diphosphate (ADP) released from platelets during collagen or AA‐induced aggregation was examined using the substrate/enzyme complex creatine phosphate/creatine phosphokinase (CP/CPK). The CP/CPK complex abolished aggregation induced by a low dose of collagen whilst aggregation to a high dose of collagen was only partially inhibited.
Aggregation induced by a high dose of collagen was abolished by a combination of CP/CPK with indomethacin or carboxyheptylimidazole.
AA‐induced aggregation was abolished by indomethacin. Carboxyheptylimidazole abolished aggregation induced by a low dose of AA but inhibition was surmounted with increasing concentrations of AA in the absence of TxA2 formation.
PGH2‐induced aggregation was unaffected by indomethacin and only partially inhibited by carboxyheptylimidazole. AA or PGH2‐induced platelet aggregation was unaffected by CP/CPK.
In conclusion, aggregation of rabbit platelets induced by a low concentration of collagen was dependent on synergism between TxA2 and ADP whilst at high concentrations of collagen, sufficient TxA2 and ADP were released to induce aggregation independently of each other.
The small amounts of prostaglandin endoperoxides produced from endogenous arachidonate have apparently no direct pro‐aggregatory role. However, the relatively large amount which can be produced by a high concentration of exogenous AA when TxA2 formation is prevented can cause aggregation of rabbit platelets.
In vivo STUDIES ON AN ANTAGONIST OF PARATHYROID HORMONE [Nle‐8, Nle‐18, Tyr‐34]bPTH‐(3–34)AMIDE
Authors: GRAY DAVID A. , PARSONS JOHN A. , POTTS JOHN T. , ROSENBLATT MICHAEL , STEVENSON RALPH W. 
Published: July 2012

The actions of parathyroid hormone (PTH) are antagonized in vitro by the peptide [Nle‐8, Nle‐18, Tyr‐34]‐bPTH‐(3–34)amide, an analogue of PTH. In this paper, the actions of the inhibitory peptide were investigated in vivo.
Native parathyroid hormone (bPTH‐(1–84)), administered i.v. (0.17–1.51 nmol in a volume of 0.3 ml) to 7 day old chicks produced hypercalcemia but administration of the analogue in doses up to 173 nmol was ineffective in this respect.
The analogue failed to antagonize the hypercalcaemia produced by bPTH‐(1–34) when injected, in 10 fold molar excess, 2 min before or simultaneously with bPTH‐(1–34).
Normocalcaemia was restored in parathyroidectomized rats by intravenous infusion of bPTH‐(1–84) at 32 pmol kg−1 h−1. Addition of the analogue to the infusion fluid in a 200 fold molar excess did not affect the concentrations of calcium and phosphate in the plasma, cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) in the urine or phosphate clearance but produced a significant (P< 0.05) rise in urinary calcium clearance.
The results suggest that the peptide [Nle‐8, Nle‐18, Tyr‐34]‐bPTH‐(3–34)amide does not antagonize the actions of PTH in vivo and demonstrate an important dichotomy between in vitro and in vivo biological properties of the PTH analogue.