bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of aspirin and prostacyclin on arrhythmias resulting from coronary artery ligation and on infarct size
Authors: Johnston Kathleen M. , MacLeod B.A. , Walker M.J.A. 
Published: July 2012

The effects of pretreatment with aspirin, and of prostacyclin (PGI2) infusions, on responses to myocardial ischaemia and infarction produced by ligation of a coronary artery were investigated in conscious rats.
Surgical preparation, under halothane anaesthesia, consisted of implanting exteriorized aortic and jugular cannulae, ECG leads and a polypropylene/polyethylene occluder for the left anterior descending coronary artery. Ligation of the coronary artery was performed six to nine days after surgery.
Aspirin pretreatment consisted of 100 mg/kg given intravenously 1 or 36 h before ligation. PGI2 infusions (10–400 ng kg−1 min−1, i.v.) were begun 2 min before ligation and continued for 4 h afterwards.
ECG, blood pressure, heart rate and arrhythmias were recorded starting 30 min before, and continuing for 4 h after, ligation. Twenty‐four hours after ligation, in surviving animals, the heart was removed for estimation of occluded and infarcted zones.
Some treatments provided antiarrhythmic and other protection in the first 30 min post‐ligation. By 4 and 24 h post‐ligation, protective effects were lost.
Both aspirin pretreatment and low doses of prostacyclin reduced arrhythmias occurring within 30 min of ligation. The highest dose of prostacylin (400 ng kg−1 min−1) was arrhythmogenic.
None of the treatments influenced the amount of cardiac tissue occluded or infarcted by ligation.
The conclusions from this study in conscious rats were that acute aspirin pretreatment and low doses of infused prostacyclin have limited beneficial actions which are mainly confined to the earliest post‐ligation period.
Non‐competitive antagonism of the α‐adrenoceptor‐mediated fast component of contraction of rat aorta, by doxazosin and prazosin
Authors: Downing O.A. , Wilson K.A. , Wilson V.G. 
Published: July 2012

α‐Adrenoceptor antagonists have been compared for their effects on dose‐response curves of fast and slow components of contraction of the rat aorta to noradrenaline (NA).
All agents caused a competitive antagonism of the slow component of contraction to NA. The order of potency was: prazosin > WB4101 = doxazosin > tiodazosin > phentolamine > corynanthine > trimazosin > rauwolscine.
For the fast component, doxazosin, prazosin, tiodazosin and WB4101 caused some depression of the maximum response. Doxazosin (25 nm) and prazosin (25 nm) produced a complete and unsurmountable antagonism of the maximum fast component. Phentolamine, corynanthine, trimazosin and rauwolscine all competitively antagonized the fast component.
The degree of antagonism of the fast component by prazosin and its analogues appeared to be directly related to the potency of individual agents for the slow component. WB4101, which was equipotent with doxazosin and more potent than tiodazosin was less effective than either in reducing the fast component.
The antagonism of the fast component by prazosin or doxazosin was easily reversed by washing and prevented by phentolamine (2.5 μm).
Neither prazosin nor doxazosin in concentrations of up to 2.5 μm had any effect on contractions of the aorta to 5‐hydroxytryptamine (5‐HT, 0.25–250 μm) or caffeine (20 mm).
It is concluded that the ability of some α‐adrenoceptor antagonists to produce a non‐competitive antagonism of the fast component of contraction is (a) dependent upon blockade of α‐adrenoceptors; (b) unrelated to selectivity for α1‐adrenoceptors; (c) related to potency and structure.
EGTA (3.0 mm) caused a selective suppression of the slow component of contraction to NA. Both doxazosin and prazosin caused a non‐competitive antagonism of EGTA‐resistant contractions to NA whereas corynanthine showed competitive antagonism. These observations, together with those above imply that prazosin and doxazosin non‐competitively antagonize α‐adrenoceptor‐induced release of calcium in the rat aorta, but competitively antagonize α‐adrenoceptor‐induced calcium entry.
Antidepressant treatments: effects in rodents on dose‐response curves of 5‐hydroxytryptamine‐ and dopamine‐mediated behaviours and 5‐HT2 receptor number in frontal cortex
Authors: Green A.R. , Heal D.J. , Johnson Pauline , Laurence B.E. , Nimgaonkar V.L. 
Published: July 2012

The effects of repeated electroconvulsive shock (ECS) administration, repeated desmethylimipramine injection (5 mg kg−1, twice daily for 14 days) and acute administration of the β‐adrenoceptor, clenbuterol, on 5‐hydroxytryptamine (5‐HT)‐ and dopamine‐mediated behaviours in mice have been examined.
All three treatments enhanced the carbidopa/5‐hydroxytryptophan (5‐HTP)‐induced head‐twitch response at all doses of 5‐HTP examined, producing a parallel shift in the dose‐response curve. A single ECS administration or single dose of desmethylimipramine had no effect.
Only repeated ECS enhanced the locomotor response to injection of apomorphine. The dose‐response curve shift was not parallel. A single ECS had no effect.
A 6‐hydroxydopamine lesion of brain dopamine terminals also enhanced the apomorphine response, but again did not produce a parallel shift in the dose‐response curve.
Both repeated ECS and repeated desmethylimipramine administration to rats increased the number of 5‐HT2 receptor sites in rat brain. Clenbuterol had no effect.
The enhancing effects of repeated ECS and clenbuterol administration on the 5‐HTP‐induced head‐twitch response were additive.
Enhanced 5‐HT‐mediated behavioural responses are seen in both mice and rats after these treatments. If it is assumed, therefore, that similar receptor changes occur in both species it appears that there is no relationship in either behavioural system between the ability of the treatment to alter receptor number and the change in the dose‐response curve (parallel or non‐parallel).
All three antidepressant treatments (ECS, a tricyclic and a β‐adrenoceptor agonist) increase 5‐HT‐mediated behavioural responses although clenbuterol did not increase 5‐HT2 receptor number. Only ECS increased dopamine‐mediated responses.
Convulsant‐induced depression of amino acid responses in cultured mouse spinal neurones studied under voltage clamp
Authors: Barker J. L. , McBurney R.N. , Mathers D. A. 
Published: July 2012

A two‐microelectrode voltage‐clamp technique was used to record membrane current responses induced by the application of the neutral amino acids, γ‐aminobutyric acid (GABA) and glycine, to mouse spinal neurones maintained in cell culture.
Membrane current responses to GABA were depressed by the convulsant agents, bicuculline, Picrotoxin and pentylenetetrazole. Membrane current responses to glycine were depressed by the convulsant compound, strychnine.
Analysis of the fluctuations in membrane current about the mean response during prolonged applications of GABA revealed that neither the conductance nor the average open‐time of GABA‐activated ion‐channels was altered in the presence of Picrotoxin or bicuculline. Pentylenetetrazole caused a reduction in the open‐time of GABA‐activated ion‐channels but this effect alone was too small to account for the depression of the current response.
A similar analysis of glycine‐induced responses in the presence of strychnine revealed that the depression of glycine responses by strychnine was not associated with any changes in the conductance or average open‐time of glycine‐activated ion‐channels.
We therefore conclude that the convulsant compounds act by reducing the rate of activation of ion‐channels by the neutral amino acids either through a reduction in the number of free receptors or by a change in the kinetics of channel activation.
β‐Adrenoceptors of the human myocardium: determination of β1 and β2 subtypes by radioligand binding
Authors: Heitz Alain , Schwartz Jean , Velly Jeanne 
Published: July 2012

β‐Adrenoceptors of the human myocardium were investigated with binding studies using 125iodocyanopindolol (ICYP) as ligand.
Inhibition of ICYP‐binding by betaxolol (a selective β1‐antagonist) and ICI 118551 (a selective β2‐blocking drug) resulted in non‐linear Scatchard‐plots suggesting that both β‐adrenoceptor subtypes are present in human left atrium and left ventricle.
Computer analysis of the data gave a β1/β2‐adrenoceptor ratio of approximately 65:35 both for left atrium and for left ventricle.
Enhancement by intracerebroventricular thyrotropin‐releasing hormone of indomethacin‐induced gastric lesions in the rat
Authors: Maeda‐Hagiwara Masaki , Watanabe Hiroshi , Watanabe Kazuo 
Published: July 2012

Effects of the intracerebroventricular thyrotropin‐releasing hormone (TRH) on gastric mucosa were studied in rats.
TRH (3 and 10 μg rat−1 i.c.v.) produced slight gastric lesions and also aggravated indomethacin‐, aspirin‐ or 5‐hydroxytryptamine (5‐HT)‐induced gastric lesions, while restraint and cold stress‐induced lesions were not influenced by TRH.
Bethanechol used at a dose sufficient to produce acid secretion did not influence the gastric mucosa in intact or indomethacin‐treated rats.
Enhancement of indomethacin‐induced gastric lesions by TRH was not inhibited to any significant degree by atropine 0.1 mg kg−1 s.c., which prevented TRH‐induced gastric acid secretion, but tended to be inhibited by phentolamine, 2.5 mg kg−1 i.p.
It is concluded that the enhancement by TRH of indomethacin‐induced gastric lesions is due to a combination of the central and peripheral actions of the ulcerogenic agents.
Contracture of guinea‐pig ileum on withdrawal of methionine5‐enkephalin is mediated by substance P
Authors: Chahl Loris A. 
Published: July 2012

The effects of methionine5‐enkephalin (Met‐enkephalin, ME) 5 × 10−8‐5 × 10−6 moll−1) were investigated on the resting guinea‐pig ileum.
While in contact with the ileum, ME reduced the natural tone and movements, but following washout a contracture occurred which increased with increasing duration of the contact period from 0.5 to 32 min and with increasing concentration of the ME present during the contact period.
The washout contractures after 2 min contact with ME, 10−6 moll−1, were abolished by naloxone, 10−6 moll−1, added prior to the addition of ME, atropine, 5 × 10−6 moll−1 and the substance P (SP) antagonist, (d‐Pro2, d‐Phe7, d‐Trp9)‐SP, 10−5 moll−1 and were reduced by 5‐hydroxytryptamine (5‐HT)‐autodesensitization. Washout contractures following 32 min contact with ME, 10−6moll−1, were significantly inhibited by the SP antagonist and naloxone and were abolished by a combination of atropine and the SP antagonist, but were not significantly reduced by atropine alone or by 5‐HT‐desensitization.
Contractures of ileum occurred on addition of naloxone to ileal segments exposed to ME for 2 or 32 min. These contractures were also inhibited by the SP antagonist but a combination of atropine and SP‐desensitization was required to abolish them.
It was concluded that gut dependence occurs following very brief exposure to an opioid and that SP plays a central role in the withdrawal response precipitated either by washout or addition of naloxone.
Studies on the stereoselectivity of the P2‐purinoceptor
Authors: Burnstock G. , Cusack N.J. , Hills J.M. , MacKenzie I. , Meghji P. 
Published: July 2012

ATP, 2‐chloro‐ATP, 2‐methylthio‐ATP, and their unnatural L‐enantiomers, were synthesized and their effects tested on the guinea‐pig taenia coli and urinary bladder, and the stimulated frog ventricle.
The potent P2‐purinoceptor agonists, 2‐chloro‐ATP and 2‐methylthio‐ATP were, respectively, 30 and 200 times more effective than ATP in relaxing the guinea‐pig taenia, but approximately as effective as ATP in contracting the guinea‐pig bladder and augmenting the force of contraction of the frog ventricle.
A high degree of stereoselectivity was observed for relaxations of the guinea‐pig taenia coli produced by the P2‐purinoceptoragonists, and 2‐methylthio‐ATP was over 700 times more effective than its L‐enantiomer. In contrast, stereoselectivity for contraction of the guinea‐pig bladder was observed only at low concentrations with each pair of enantiomers, and a similar low stereoselectivity was displayed by the frog ventricle.
These results show that P2‐purinoceptors mediating inhibitory responses in the guinea‐pig taenia coli can show a high degree of stereoselectivity, while P2‐purinoceptors mediating excitatory responses in the guinea‐pig bladder and in the frog ventricle show little stereoselectivity.
The partial stereoselectivity of the P2‐purinoceptor in smooth muscle contrasts with the absolute stereospecificity of P1‐purinoceptors for adenosine on smooth muscle and autonomic nerve terminals and the absolute stereospecificity of the receptor for ADP on the human platelet.
Effect of inhibition of synthesis and receptor antagonism of SRS‐ A in cardiac anaphylaxis
Authors: Aehringhaus U. , Peskar B.A. , Wittenberg H.R. , Wölbling R.H. 
Published: July 2012

The effects of infusions of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 1.1 × 10−7 mol min−1) and the antagonist of slow‐reacting substance of anaphylaxis (SRS‐A) FPL 55712 (1.2 × 10−7molmin−1) on the coronary constriction and the release of SRS‐A, leukotriene C4‐like immunoreactivity, thromboxane B2 and 6‐keto‐prostaglandin F1α from perfused anaphylactic guinea‐pig hearts were investigated.
Both NDGA and FPL 55712 in the concentrations used induced an increase in basal coronary flow, but did not prevent the coronary flow reduction in the early phase (0–4 min) after antigen injection. On the other hand, NDGA and FPL 55712 inhibited the less pronounced long‐lasting coronary flow reduction in the later phase of cardiac anaphylaxis.
NDGA decreased the release of SRS‐A from the anaphylactic guinea‐pig hearts below or close to the detection limit of the bioassay and simultaneously diminished the release of leukotriene C4‐like immunoreactivity. On the other hand, FPL 55712 did not influence the amounts of leukotriene C4‐like immunoreactivity released in cardiac anaphylaxis.
Neither NDGA nor FPL 55712 affected the release of immunoreactive thromboxane B2 (TXB2) from anaphylactic guinea‐pig hearts. Release of 6‐keto‐prostaglandin F1α after challenge, however, was decreased by NDGA, while FPL 55712 had no significant effect.
These results suggest, that SRS‐A may be a relatively more important mediator in the late phase of coronary constriction occurring during cardiac anaphylaxis, while the effects of other mediators, particularly vasoconstrictor cyclo‐oxygenase products, seem to prevail in the early phase.
Inhibition by purines of the inotropic action of isoprenaline in rat atria
Authors: Hughes P.R. , Stone T.W. 
Published: July 2012

The effects of a series of adenosine derivatives were examined on the catecholamine‐stimulated electrically‐driven rat left atrium in vitro.
All the purines tested reduced the positive inotropic action of isoprenaline, 0.1 μM, with the potency order: L‐N6‐phenlylisopropyladenosine (L‐PIA) > 5′‐N‐ethylcarboxamide adenosine (NECA) > D‐PIA > 2‐chloroadenosine > adenosine. Dipyridamole did not change the IC50 of adenosine. The adenosine deaminase inhibitor, 2′deoxycoformycin, produced a small but nonsignificant shift to the left of the adenosine concentration‐response curve.
The cardiac depressant effects of these purines were reversed by theophylline and the IC50 values were unchanged in the presence of atropine or in atria taken from reserpine‐treated rats.
It is concluded that the purine receptor mediating these effects should not be classified on the A1/A2 system. The relationship between functionally characterized purine receptors and those originally defined as modulating adenylate cyclase is discussed.
Nicotine self‐administration in rats
Authors: Cox Brian M. , Goldstein Avram , Nelson William T. 
Published: July 2012

Female Wistar rats were allowed to self‐administer nicotine solutions through indwelling jugular vein cannulae for 23 h per day for periods from three to five weeks.
Two response levers were available to the rats; responding on one lever, designated the active lever, produced an immediate infusion of nicotine solution or saline. A second lever for which responding had no programmed consequences was introduced as a control for the locomotor stimulant action of low doses of nicotine.
Baseline lever response rates were determined over a period of one week, in which active lever responding produced an infusion of saline. Rats were then allowed access to varying doses of nicotine or saline for a further two or three weeks. Response rates on the active lever increased significantly in rats with access to nicotine at a dose of 30 μg kg−1 per response. However, control lever response rates were also significantly elevated.
The role of nicotine‐induced locomotor stimulation in the self‐administration behaviour was further evaluated in a dose‐reduction experiment, in which the dose of nicotine available to rats responding for 30 μg kg−1 per response was reduced to 3 μg kg−1 per response. This resulted in a significant differential increase in active lever responding relative to control lever responding.
The results suggest that nicotine is positively reinforcing in rats which had not previously been deprived of food or water or received prior drug treatment, but also indicate that nicotine induced locomotor stimulation may contribute to the observed increases in lever response rates when rats self‐administer nicotine.
Calcium‐dependence and antagonism of responses to α1‐ and α2‐adrenoceptor agonists in vascular tissues from hypertensive and normotensive rats
Authors: Rutledge A. , Swamy V.C. , Triggle D.J. 
Published: July 2012

Inhibition by D600 (methoxyverapamil) of responses to an α2‐adrenoceptor selective agonist, B‐HT 920, (6‐allyl‐2‐amino‐5, 6, 7, 8‐tetrahydro‐4H‐thiazolo [4, 5‐d] azepin dihydrochloride), an α1‐adrenoceptor selective agonist, phenylephrine (PE), and a nonselective agonist, noradrenaline (NA), was studied in isolated preparations of the aortae and carotid arteries obtained from young (5–7 weeks) and old (15–17 weeks) hypertensive (SHR) and normotensive (WKY) rats.
Maximum responses of WKY tissues to B‐HT 920 were the most sensitive, PE‐induced responses the least sensitive and maximum responses to NA were intermediate in their sensitivity to inhibition by D600.
Sub‐maximal responses to NA and PE were not different in their sensitivity to inhibition by D600, but were less sensitive than the responses to B‐HT 20. Sub‐maximal responses to PE were significantly more sensitive to D600 inhibition than were the maximal responses to this agonist.
NA‐induced responses of tissues from older SHR were less sensitive to inhibition by D600 when compared to responses in WKY rats.
Responses to B‐HT 920, in tissues suspended in calcium‐free solutions, showed the largest decline compared to NA‐ and PE‐induced responses.
We conclude that responses to B‐HT 920 largely utilize extracellular calcium. PE‐ and NA‐induced responses mobilize extracellular calcium to varying degrees depending upon the concentration of the agonist employed to elicit the response.
Comparison of s‐ and κ‐ opiate receptor ligands as excitatory amino acid antagonists
Authors: Berry S.C. , Dawkins S.L. , Lodge D. 
Published: July 2012

Using the technique of microelectrophoresis in pentobarbitone‐anaesthetized cats and rats, the effects of benzomorphans, with known actions at s‐ and κ‐ opioid receptors, were tested on responses of spinal neurones to amino acids and acetylcholine.
The racemic mixture and both enantiomers of the sigma opiate receptor agonist, N‐allylnormetazocine (SKF 10,*** 047), and the dissociative anaesthetic, ketamine, reduced or abolished excitation evoked by N‐methyl‐aspartate (NMA) with only small and variable effects on responses to quisqualate or kainate. (+)‐SKF 10,***047 was 1.2 ± 0.7 times more potent than the (—) enantiomer in antagonizing NMA.
On Renshaw cells, (+)‐SKF 10,***047 enhanced responses to acetylcholine whereas the (—) enantiomer produced only a small reduction.
The κ‐ opiate receptor agonist, ethylketocyclazocine, had no selective effects on responses to amino acids or to acetylcholine.
We conclude that actions at s‐ but not κ‐, opiate receptors are responsible for the NMA antagonism observed with benzomorphans.
5‐HT2 receptor characteristics in frontal cortex and 5‐HT2 receptor‐mediated head‐twitch behaviour following antidepressant treatment to mice
Authors: Goodwin Guy M. , Green A. Richard , Johnson Pauline 
Published: July 2012

The effects of repeated administration of antidepressant drugs or electroconvulsive shock on the binding of [3H]‐spiperone to the 5‐hydroxytryptamine2 (5‐HT2) receptor in mouse frontal cortex and the 5‐HT‐mediated head‐twitch response have been examined.
Repeated electroconvulsive shock increased both the head‐twitch response and the number of 5‐HT2 binding sites (Bmax).
After 35 d but not 24 h or 14 d oral tranylcypromine (5.6 mg kg−1 per day) there was a marked decrease in both the behavioural response and the number of 5‐HT2 receptors.
Repeated oral doses of zimeldine (20 mg kg−1 per day, 14 days) also decreased the head‐twitch response and the number of 5‐HT2 binding sites and these effects persisted after 48 h withdrawal.
Oral mianserin (2.1 mg kg−1 per day, 14 days) decreased both the behaviour and the number of 5‐HT2 binding sites, but this change was also seen after acute (1 day) administration. After 48 h withdrawal from chronic treatment the head‐twitch response was still decreased but the Bmax had returned to control values.
Desipramine given orally (27 mg kg−1 per day, 14 days) decreased both the behaviour and number of 5‐HT2 binding sites. After 48 h withdrawal, binding was still decreased but the head‐twitch response was enhanced above control values.
In contrast to repeated electroconvulsive shock (ECS), all drugs decreased both 5‐HT2 binding and the head‐twitch response, while the mice were still on treatment. Binding and behaviour did not correlate after withdrawal. It is concluded that antidepressant treatments do not produce a common alteration in 5‐HT2 receptor number and function.