bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory actions of opioid compounds on calcium fluxes and neurotransmitter release from mammalian cerebral cortical slices
Authors: Bradford H.F. , Crowder J.M. , White E.J. 
Published: July 2012

The effects of opioid agonists on veratrine‐stimulated Ca2+ influx and amino acid neurotransmitter release in rat cerebrocortical brain slices were studied. Inhibitory effects were seen on both of these parameters with all of the opioid agonists used.
None of the drugs used affected basal 45Ca2+ uptake, basal K+ content or basal amino acid release from the slices.
At high concentrations (100 μM) fentanyl, tifluadom, U50,488H, butorphanol and bremazocine greatly inhibited the depolarization of the slices by veratrine as determined by the reduced release of K+.
The opioid receptor subtypes at which the drugs were acting were characterized by the antagonistic effects of naloxone and WIN44441‐3.
The opioid‐induced inhibition of stimulated Ca2+ uptake and amino acid release were not antagonized by WIN44441‐2, the inactive enantiomer of WIN44441‐3.
It is concluded that opioid agonists acting through μ‐ and k‐receptors and probably through δ‐ and s̀‐receptors, have an inhibitory effect on Ca2+ uptake into cerebrocortical brain slices and the subsequent release of aspartate, glutamate and γ‐aminobutyric acid (GABA).
The anaphylactic release of platelet‐activating factor from perfused guinea‐pig lungs
Authors: Fitzgerald Mary F. , Moncada Salvador , Parente Luca 
Published: July 2012

The release of platelet‐activating factor (Paf‐acether) and of its inactive precursor/metabolite lysoplatelet activating factor (lyso‐Paf) from control and sensitized guinea‐pig isolated lungs challenged with antigen was investigated.
Control guinea‐pig lungs perfused either through the pulmonary circulation or through the airways and challenged with antigen did not release Paf‐acether.
Sensitized guinea‐pig isolated lungs perfused through the pulmonary circulation and challenged with antigen released lyso‐Paf but not Paf‐acether.
Sensitized guinea‐pig isolated lungs perfused through the airways and challenged with antigen released three times more lyso‐Paf and also Paf‐acether.
These results support a possible role for Paf‐acether in respiratory anaphylaxis in the guinea‐pig.
Postjunctional inhibition of contractor responses in the mouse vas deferens by rat and human calcitonin gene‐related peptides (CGRP)
Authors: Al‐Kazwini S.J. , Craig R.K. , Marshall I. 
Published: July 2012

The effects of rat and human α‐calcitonin gene‐related peptide (CGRP) were compared in the mouse and rabbit isolated vas deferens preparation contracted by either field stimulation or acetylcholine.
The peptides were about equipotent at inhibiting twitch responses of the mouse vas deferens to field stimulation at 0.2 Hz (IC50 12 ± 4 nM and 15 ± 3 nM, rat and human α‐CGRP respectively). Rat α‐CGRP was less potent at inhibiting responses to 10 Hz than to either 0.2 Hz or 1.0 Hz stimulation. The potency of rat α‐CGRP at 1.0 Hz was unaltered by halving the calcium concentration of the Krebs solution.
The inhibitory effect of human α‐CGRP was not antagonized by either propranolol (300 nM) or idazoxan (300 nM), although in the same tissues these latter two drugs reduced responses to isoprenaline and clonidine respectively.
Rat α‐CGRP (100 nM) and human α‐CGRP (1.0 μM) did not alter the uptake of [3H]‐noradrenaline (30 nM) into mice isolated vasa deferentia. Rat α‐CGRP (3–100 nM) did not alter the fractional release per pulse (1.0 Hz, 100 pulses) of tritium from vasa preloaded with [3H]‐noradrenaline, although at the same time the peptide inhibited responses of the smooth muscle to field stimulation.
Rat and human α‐CGRP were equipotent at inhibiting contractions of the mouse vas deferens evoked by acetylcholine although the peptides were less potent than against twitch responses.
In the rabbit vas deferens neither rat nor human α‐CGRP (3 nM‐1 μM) inhibited either twitch responses or acetylcholine contractions.
These results suggest that rat and human α‐CGRP inhibit contractor responses of the mouse vas deferens not by interference with adrenergic mechanisms, but through postjunctional (possibly CGRP) receptors. A similar mechanism may underlie effects of CGRP in other tissues. The rabbit vas deferens appears to lack the CGRP ‘receptors’.
Effect of the adenosine antagonist 8‐phenyltheophylline on glycerol‐induced acute renal failure in the rat
Authors: Bowmer C.J. , Collis M.G. , Yates M.S. 
Published: July 2012

8‐Phenyltheophylline (8‐PT) (10 mg kg−1) or its vehicle (1 ml kg−1) were administered intravenously or intraperitoneally twice daily over 48 h to rats with acute renal failure (ARF) induced by intramuscular (i.m.) injection of glycerol.
Rats treated with 8‐PT i.v. had significantly lower plasma urea and creatinine levels at 24 and 48 h compared to untreated animals.
The vehicle also reduced plasma urea and creatinine when compared to untreated controls. However, plasma urea levels in 8‐PT‐treated rats were significantly lower than in vehicle‐treated animals at 24 and 48 h after both i.v. and i.p. administration. Plasma creatinine concentrations also tended to be lower in the 8‐PT‐treated group.
[3H]‐inulin clearance at 48 h after i.m. glycerol was significantly greater in rats dosed i.p. with 8‐PT compared to either untreated or vehicle treated rats.
Examination of kidneys taken from rats 48 h after i.m. glycerol showed that 8‐PT treatment significantly reduced renal damage and kidney weight compared to the untreated or vehicle‐treated groups.
In a 7 day study all the rats which received 8‐PT i.p. survived whilst in the vehicle and untreated groups the mortality rates were 12 and 21% respectively.
In a separate series of experiments 8‐PT (10 mg kg−1; i.v. or i.p.) was found to antagonize adenosine‐induced bradycardia in conscious rats for up to 5 h.
There is no clear explanation for the partial protection afforded by the vehicle but it may be related to either its alkalinity or an osmotic effect produced by the polyethylene glycol component.
The protective effect of 8‐PT in rats with ARF was probably the result of adenosine antagonism.
Effects of calcium, calcium entry blockers and calmodulin inhibitors on atrioventricular conduction disturbances induced by hypoxia
Authors: Anno Takafumi , Kodama Itsuo , Shibata Shoji , Toyama Junji , Yamada Kazuo 
Published: July 2012

Effects of hypoxia on atrioventricular conduction were investigated in the Langendorff‐perfused isolated heart of the rabbit with various extracellular calcium concentrations ([Ca2+]) as well as in the presence of verapamil, nifedipine, N‐(6‐aminohexyl)‐5‐chloro‐1‐naphthalenesulphonamide (W‐7) and chlorpromazine.
The prolongation of the atrio‐His (AH) interval by hypoxia for 7 min was greater with increasing [Ca2+]o ranging from 1.2 to 5.2 mM. At [Ca2+]o of over 3.2 mM under hypoxic conditions, AH block of the Wenckebach type was observed in some cases.
Verapamil (5 × 10−8 M) and nifedipine (5 × 10−8 M) caused a significant prolongation of AH intervals before hypoxia. However, the intensity of AH prolongation due to hypoxia was significantly attenuated in the presence of the calcium entry blocker, and AH block was not induced even at 3.2 mM [Ca2+]o.
W‐7 (5 × 10−6M) and chlorpromazine (10−6M) did not affect the AH intervals before hypoxia. The hypoxia‐induced prolongation of the AH interval or AH block was prevented in the presence of these drugs.
W‐5, a chlorine‐deficient derivative of W‐7, showed no protection against hypoxia‐induced AV nodal conduction disturbances.
These findings suggest that hypoxia‐induced AV nodal conduction disturbance is explained, at least in part, by the electrical uncoupling of nodal cells, probably due to the calcium overload. This conduction disturbance is protected by calcium entry blockers or by calmodulin inhibitors, but the mode of protective action is not the same for these different categories of drugs.
Catecholamine release and potentiation of thromboxane A2 production by nicotine in the greyhound
Authors: Dusting G.J. , Li D.M.F. 
Published: July 2012

Thromboxane A2 was generated by infusing arachidonic acid (2.5 μg ml−1) into an extra‐corporeal circuit of blood withdrawn from anaesthetized dogs, and assayed on a blood‐bathed bioassay cascade of porcine and bovine coronary artery strips, chick rectum and rat stomach strip. All tissues except chick rectum were treated with phentolamine and propranolol to abolish direct effects of catecholamines.
The arachidonate‐induced contractions of artery strips were abolished by a thromboxane synthetase inhibitor UK‐38485 (3 mg kg−1, i.v.), but were not altered by the 5‐hydroxytryptamine antagonist ketanserin (10 μM) administered over the tissues.
Intravenous infusion of adrenaline (0.2 and 0.4 μg kg−1 min−1) reversibly potentiated the coronary contractions produced by arachidonate, but did not alter contractions when applied directly over the bioassay tissues.
Intra‐aortic infusion of nicotine (5 or 10 μg kg−1 min−1) also increased the arachidonate‐induced contractions of the bioassay tissues but only on those experiments where nicotine caused appreciable adrenaline release, as indicated by relaxation of chick rectum.
Phenoxybenzamine (2 mg kg−1, i.v.) blocked the potentiation effect of adrenaline and nicotine on coronary contractions. The specific α2‐adrenoceptor antagonist, idazoxan (1 mg kg−1, i.v.), also blocked nicotine‐induced potentiation of the contractions.
These findings suggest that the ability of nicotine to potentiate thromboxane release from circulating platelets and blood cells is dependent upon the release of adrenaline, and probably involves an action on α‐adrenoceptors of the circulating blood elements.
A comparison of the acute inflammatory response in adrenalectomised and sham‐operated rats
Authors: Flower R.J. , Parente L. , Persico Paola , Salmon J.A. 
Published: July 2012

Carrageenin pleurisy was induced in adrenalectomised (ADX) and sham‐operated (SHO) rats.
The magnitude and duration of inflammation, as estimated by fluid exudation and cell migration, was greatly increased (approximately doubled) in ADX rats compared with that in their SHO controls.
The content of eicosanoids (6‐keto‐prostaglandin F1α (6‐keto‐PGF1α), thromboxane B2 (TXB2), and leukotriene B4 (LTB4)) in inflammatory exudates from ADX rats was significantly (2–4 fold) greater than that of their SHO controls.
Resident macrophages obtained from ADX rats produced more eicosanoids per cell per unit time when stimulated in vitro with zymosan, than did cells from the SHO controls.
Administration of glucocorticoids blocked the inflammatory response and reduced the release of eicosanoids both in vitro and in vivo in both groups of rats.
These data are consistent with the notion that physiological amounts of glucocorticoids exert a tonic inhibitory action on phospholipase activity in normal animals and that the increased secretion of these hormones during the inflammatory response serves to check and control the development of inflammation.
An examination of the pharmacology of two substance P antagonists and the evidence for tachykinin receptor subtypes
Authors: Bailey S.J. , Featherstone R.L. , Jordan C.C. , Morton I.K.M. 
Published: July 2012

The potencies of two tachykinin antagonists [D‐Pro4, D‐Trp7,9,10]‐SP(4–11) and [D‐Arg1, D‐Pro2, D‐Trp7,9, Leu11]‐SP(1–11) against four tachykinins were examined in a range of smooth muscle preparations, including guinea‐pig ileum and bladder and rat colon muscularis mucosae and duodenum.
Parallel shifts in the log dose‐response curves of all the tachykinins tested were observed in all tissues, except in the case of the guinea‐pig bladder where [D‐Pro4, D‐Trp7,9,10]‐SP(4–11) was without effect at concentrations up to 32 μM.
The slopes of the Schild plots for the two antagonists did not differ significantly from unity, with the exception of [D‐Pro4, D‐Trp7,9,10]‐SP(4–11) in the rat duodenum, which may indicate a heterogeneous receptor population in this tissue. The antagonists displayed agonist selectivity in the case of the guinea‐pig ileum where log dose‐response curves to substance P and physalaemin were shifted less than those to eledoisin and kassinin.
Rank orders of potency for eledoisin, kassinin, physalaemin and substance P in the five preparations studied allowed classification of the tissues by the predominant receptor type according to the ‘SP‐P’ and ‘SP‐E’ scheme.
It is concluded that [D‐Pro4, D‐Trp7,9,10]‐SP(4–11), in particular, displays tissue selectivity that may indicate different receptor populations, but classification of receptor and tissue types on this basis does not fully correspond with classifications based on agonist potencies. Such schemes should therefore be treated with caution at this stage.
A comparison of motor behaviours in groups of rats distinguished by their climbing response to apomorphine
Authors: Davis A.S. , Jenner P. , Marsden C.D. 
Published: July 2012

Administration of apomorphine hydrochloride (0.5 mg kg−1 s.c.) to adult male or female Wistar rats previously acclimatized to the test environment induced climbing behaviour in approximately 50% of animals examined. The proportion of animals climbing was related to age, being maximal at 8–9 weeks.
Those animals showing an initial climbing response to apomorphine (0.5 mg kg−1 s.c), climbed when challenged with this dose of apomorphine on subsequent occasions. In ‘climbing’ animals the intensity of response was related to the dose of apomorphine administered; no dose‐response relationship was observed in ‘non‐climbing’ animals.
No overall differences in the spontaneous motor behaviour of ‘climbing’ and ‘non‐climbing’ animals were apparent as assessed by measurement of spontaneous climbing behaviour, by holeboard activity, and by locomotor activity measured in either photocell cages or in a treadwheel.
There was no overall difference in the ability of apomorphine to induce locomotor activity or stereotyped behaviour in ‘climbing’ and ‘non‐climbing’ animals. However, the administration of apomorphine induced rearing and treadwheel activity only in those animals classified as ‘climbers’.
There was no difference between the number (Bmax) of specific [3H]‐spiperone binding sites or the dissociation constant (KD) in striatal or mesolimbic tissue preparations for ‘climbing’ and ‘non‐climbing’ rats.
The ability of an animal to climb in response to apomorphine appears to be dependent on an ability to orient vertically, since this is a component of behaviour common to climbing, rearing, and treadwheel activity. The ability to climb does not appear to be related to differences in dopamine receptor numbers in brain or to the penetration of apomorphine into brain.
Identification of selective, high affinity [125I]‐angiotensin and [125I]‐bradykinin binding sites in rat intestinal epithelia
Authors: Cox Helen M. , Munday Kenneth A. , Poat Judith A. 
Published: July 2012

Specific [125I]‐angiotensin II (AII) and [125I]‐bradykinin (Bk) binding sites have been identified within epithelial membranes from rat jejunum and descending colon.
These high affinity intestinal sites exhibited KD values of 0.64 ± 0.16 nM for [125I]‐AII and 0.69 ± 0.13 nM for [125I]‐Bk, which were similar to those for [125I]‐AII (0.85 nM) and [125I]‐Bk binding sites (1.03 nM) previously identified in renal cortex epithelia.
Specific [125I]‐AII binding capacity was only 19.77 ± 2.74 fmol mg−1 in small intestine and 11.31 ± 2.66 fmol mg−1 in descending colon epithelia while a larger population, 332.0 ± 72.9fmol‐mg−1 of specific [125I]‐Bk sites were identified in epithelial membranes from small intestine.
Significant hydrolysis of both free [125I]‐AII and [125I]‐Bk was observed while membrane bound peptides remained relatively resistant to degradation. Whilst no corrections have been made to the observed values of KD and Bmax quoted above, one may assume that the calculated reductions in the free hormone concentration will result in a decrease of the KD value for both peptides. Loss of membrane bound peptide, particularly of [125I]‐AII, may indicate that the calculated Bmax value is an underestimation.
Despite the rapid degradation of unbound [125I]‐AII and [125I]‐Bk during incubations the kinetics of specific peptide binding were reversible and highly selective. The order of potency for specific [125I]‐AII binding was [Sar1, Leu8]‐AII > [Sar1, Thr8]‐AII > AII > [Sar1, Ile8]‐AII > [Des, Asp1, Ile8] AII > AIII. Specific [125I]‐Bk binding was also highly selective, the order of potency being Phe8‐Bk>Tyr8‐Bk>Lys‐Bk>Des, Arg1‐Bk. AII exhibited an IC50 of > ImM for specific [125I]‐Bk binding and likewise Phe8‐Bk for specific [125I]‐AII binding.
The determination of receptor constants for histamine H2‐agonists in the guinea‐pig isolated right atrium using an irreversible H2‐antagonist
Authors: Rising T. J. , Steward A. 
Published: July 2012

From measurements of chronotropy in the guinea‐pig isolated right atrium, a compound (E1309) was found which behaved as an irreversible antagonist at the histamine H2 receptor.
E1309 was used to block irreversibly a proportion of the H2 receptors and the dissociation constants, relative efficacies and receptor reserves of four H2‐agonists were determined.
The calculated dissociation constants were similar to the Ki values reported from H2‐radioligand binding studies but different from the observed EC50 values.
The order of potency for the four H2‐agonists was impromidine > > histamine > dimaprit> 4‐methylhistamine.
The order of relative efficacy was 4‐methylhistamine > dimaprit > histamine > impromidine, the natural agonist not being the most efficacious. This atypical finding is discussed in relation to other receptor classes.
Studies on the receptor mediating cyclic AMP‐independent enhancement by adenosine of IgE‐dependent mediator release from rat mast cells
Authors: Church Martin K. , Hughes Philip J. , Vardey Christopher J. 
Published: July 2012

Adenosine produced a concentration‐related enhancement of antigen‐induced 5‐hydroxytryptamine (5‐HT) release from rat serosal mast cells. This potentiation was maximal following the simultaneous addition of adenosine with antigen.
Enhancement of 5‐HT release was accompanied by potentiation of the adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) response to challenge. The cyclic AMP response, which was antagonized by 8‐phenyltheophylline, was characterized as an A2‐purinoceptor‐mediated effect by the use of 5′‐N‐ethylcarboxamideadenosine (NECA) and L‐N6‐phenylisopropyladenosine (L‐PIA).
Enhancement of 5‐HT release, conversely, was not blocked by 8‐phenyltheophylline suggesting it to be mediated by a cyclic AMP‐independent mechanism.
The effect of adenosine on 5‐HT release was not reduced by the inhibition of the facilitated uptake of adenosine with dipyridamole, hexobendine or p‐nitrobenzylthioguanosine, therefore, suggesting it to be mediated by a cell surface receptor.
The receptor mediating enhancement of 5‐HT does not appear to belong to the P2‐purinoceptor subtype as adenosine was more potent than both adenosine monophosphate (AMP) and adenosine diphosphate (ADP) and α,β‐methylene ATP was inactive. Furthermore, the effects of AMP were blocked by α,β‐methylene ADP, which inhibits the conversion of AMP to adenosine.
Adenosine, NECA, L‐ and D‐PIA were all of equal potency in enhancing 5‐HT release. Inosine and 3‐deazaadenosine were also active. The rank order of potency of these adenosine analogues is not consistent with an effect at A1‐ or A2‐purinoceptors.
There appear to be two adenosine receptors on rat mast cells, an A2‐purinoceptor which stimulates adenylate cyclase and a separate purinoceptor, stimulation of which produces enhancement of mediator release by an unknown mechanism. The effects mediated by these receptors appear to be independent of each other.
Anaesthesia abolishes the effect of valproate on extracellular 5‐HIAA, DOPAC and ascorbate as measured in rat striatum by differential pulse voltammetry
Authors: Crespi F. , Keane P.E. , Morre M. 
Published: July 2012

The effect of sodium valproate (VPA, 400 mg kg−1, i.p.) on extracellular ascorbate, 3,4‐dihydroxyphenylacetic acid (DOPAC) and 5‐hydroxyindoleacetic acid (5‐HIAA) in the striatum was examined by differential pulse voltammetry in anaesthetized and freely‐moving rats.
In rats anaesthetized with chloral hydrate (400 mg kg−1, i.p.), pentobarbitone (50 mg kg−1, i.p.) or phenobarbitone (60 mg kg−1, i.p.), VPA produced no significant changes in peak 1 (extracellular ascorbate) or peak 2 (extracellular DOPAC), but produced a slight but statistically significant reduction in the height of peak 3 (extracellular 5‐HIAA).
In contrast, in freely‐moving rats the same dose of VPA greatly reduced extracellular ascorbate and DOPAC concentrations, and increased that of 5‐HIAA.
These results suggest that VPA may reduce the release or turnover of dopamine, and increase that of 5‐hydroxytryptamine in conscious rats. Our data also suggest that caution may be required in the interpretation of the effects of VPA in anaesthetized animals, as the results obtained may not always reflect the situation in the absence of anaesthesia.
The effect of enalapril (MK421), an angiotensin converting enzyme inhibitor, on the conscious pregnant ewe and her foetus
Authors: Pipkin Fiona Broughton , Wallace Carol P. 
Published: July 2012

The effects of enalapril, an angiotensin converting enzyme (ACE) inhibitor, on maternal and foetal blood pressure, heart rate and components of the renin‐angiotensin‐aldosterone system were studied in 9 chronically‐cannulated pregnant ewes and their foetuses.
Six ewes received 1 mg kg−1 enalapril i.v. while 3 were given 2 mg kg−1. Although the initial fall in blood pressure was slightly greater in the higher dose group, there was substantial overlap of data. The pressor response to angiotensin I, assessing ACE activity, was abolished within 10 min of administration, and did not recover during 3 h of observation. Maternal systolic and diastolic pressures reached a nadir 90 min after administration (P < 0.001, P < 0.002 respectively). The maximum tachycardia was seen at 60 min (P < 0.05).
The foetuses of the ewes given 1 mg kg−1 enalapril showed no change in systolic or diastolic blood pressure or heart rate. Those of the ewes given the higher dose showed late‐onset hypotension, coincident with the lowest maternal blood pressures.
Maternal plasma renin concentration (PRC) had risen significantly by 30 min (P < 0.02), reaching a maximum at approximately 90 min. Maternal plasma angiotensin II and aldosterone concentrations both fell initially (P < 0.05) but were almost at basal levels by the end of the experiment.
Foetal plasma renin, angiotensin II and aldosterone concentrations were unchanged throughout the experiment.
Peak values of enaprilic acid, the active principle, were recorded in maternal plasma 65–90 min after administration of 1 mg kg−1, and 25–30 min after the administration of 2 mg kg−1. A trace amount of the active principle was recorded in the foetal plasma of one lamb, whose mother had been given the higher dose. None was recorded in the plasma from three other lambs.
Maternal plasma ACE concentrations fell by an average of 84%; in 4 of the 6 ewes in which concentrations were measured they were undetectable after treatment. Foetal plasma ACE concentrations were unchanged throughout.
Enalapril at 1 mg kg−1 thus exerts a depressor effect on the pregnant ewe which is probably related to its blockade of the renin‐angiotensin system. Both direct measurement of the drug and foetal observation suggest that it does not cross the sheep placenta at this dose. This is consistent with its failure to cross the blood‐brain barrier. Foetal effects were noted at 2 mg kg−1, and there was an unexpected foetal death in this group.