British journal of pharmacology.
Publisher:
Macmillian Journals Ltd.. London : Wiley
Frequency: Twenty four no. a year
Country: England
Language: English
Author(s):
British Pharmacological Society., Proceedings of the British Pharmacological Society.
Start Year:1968 -
ISSN:
0007-1188 (Print)
1476-5381 (Electronic)
0007-1188 (Linking)
1476-5381 (Electronic)
0007-1188 (Linking)
Impact Factor
7.3
2023
| NLM ID: | 7502536 |
| (DNLM): | B35160000(s) |
| (OCoLC): | 01240522 |
| Coden: | BJPCBM |
| LCCN: | sn 83002971 |
| Classification: | W1 BR601 |
Effect of selective IK,ACh inhibition by XAF-1407 in an equine model of tachypacing-induced persistent atrial fibrillation. Inhibition of the G-protein gated ACh-activated inward rectifier potassium current, IK,ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF. The pharmacological ion channel profile of XAF-1407 was investigated us...
Contractile effects of 5-hydroxytryptamine and 5-carboxamidotryptamine in the equine jejunum. The use of human prokinetic drugs in colic horses leads to inconsistent results. This might be related to differences in gastrointestinal receptor populations. The motor effects of 5-hydroxytryptamine (5-HT; serotonin) on the equine mid-jejunum were therefore studied. Longitudinal muscle preparations were set up for isotonic measurement. 5-HT induced tonic contractions with superimposed phasic activity; these responses were not influenced by tetrodotoxin and atropine, suggesting a non-neurogenic, non-cholinergic pathway. The 5-HT receptor antagonists GR 127935 (5-HT(1B,D)), ketanserin (5-HT(2A...
Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries. The distribution of neuropeptide Y (NPY)-immunorective nerves and the receptors involved in the effects of NPY upon electrical field stimulation (EFS)- and noradrenaline (NA)-elicited contractions were investigated in horse penile small arteries. NPY-immunoreactive nerves were widely distributed in the erectile tissues with a particularly high density around penile intracavernous small arteries. In small arteries isolated from the proximal part of the corpora cavernosa, NPY (30 nM) produced a variable modest enhancement of the contractions elicited by both EFS and NA. At the same concentration...
Distinct roles of GPVI and integrin alpha(2)beta(1) in platelet shape change and aggregation induced by different collagens. 1. Various platelet membrane glycoproteins have been proposed as receptors for collagen, in some cases as receptors for specific collagen types. In this study we have compared the ability of a range of collagen types to activate platelets. 2. Bovine collagen types I-V, native equine tendon collagen fibrils and collagen-related peptide (CRP) all induced platelet aggregation and shape change. 3. Responses were abolished in FcRgamma chain-deficient platelets, which also lack GPVI, indicating a critical dependence on the GPVI/FcRgamma chain complex. 4. Responses to all collagens were unaffected in...
Contribution of K+ channels and ouabain-sensitive mechanisms to the endothelium-dependent relaxations of horse penile small arteries. 1. Penile small arteries (effective internal lumen diameter of 300 600 microm) were isolated from the horse corpus cavernosum and mounted in microvascular myographs in order to investigate the mechanisms underlying the endothelium-dependent relaxations to acetylcholine (ACh) and bradykinin (BK). 2. In arteries preconstricted with the thromboxane analogue U46619 (3-30 nM), ACh and BK elicited concentration-dependent relaxations, pD2 and maximal responses being 7.71+/-0.09 and 91+/-1 % (n=23), and 8.80+/-0.07 and 89+/-2% (n=24) for ACh and BK, respectively. These relaxations were abolished by me...
Involvement of nitric oxide in the non-adrenergic non-cholinergic neurotransmission of horse deep penile arteries: role of charybdotoxin-sensitive K(+)-channels. 1. The involvement of nitric oxide (NO) and the signal transduction mechanisms mediating neurogenic relaxations were investigated in deep intracavernous penile arteries with an internal lumen diameter of 600-900 microns, isolated from the corpus cavernosum of young horses. 2. The presence of nitric oxide synthase (NOS)-positive nerves was examined in cross and longitudinal sections of isolated penile arteries processed for NADPH-diaphorase (NADPH-d) histochemistry. NADPH-d-positive nerve fibres were observed in the adventitia-media junction of deep penile arteries and in relation to the trabec...
Functional and ligand binding studies suggest heterogeneity of platelet prostacyclin receptors. 1. This study describes attempts to compare prostacyclin (IP-) receptors in human, pig, horse, rabbit and rat platelets and in circular muscle of human, rabbit and dog mesenteric and pig gastroepiploic arteries. Three stable prostacyclin analogues, iloprost, cicaprost and 6a-carba-prostacyclin (6a-carba-PGI2) and a prostaglandin endoperoxide analogue EP 157 (previously shown to mimic prostacyclin on human platelets) were used. 2. Our main conclusion is that prostacyclin receptors on human, pig and horse platelets are similar in nature, but distinct from those on rabbit and rat platelets. Funct...
(+)-[3H]-PN 200-110 binding to cell membranes and intact strips of portal vein smooth muscle: characterization and modulation by membrane potential and divalent cations. 1. Specific binding of the calcium-antagonist dihydropyridine derivative, (+)-[3H]-PN 200-110 (isradipine), to cell membranes of equine portal vein smooth muscle was compared with binding to intact strips isolated from rat portal veins. 2. Specific binding to vascular smooth muscle membranes was of high affinity, saturable and reversible. The dissociation constant obtained from association and dissociation kinetics of (+)-[3H]-PN 200-110 was similar to that obtained from equilibrium binding and competition experiments. 3. Specific binding of (+)-[3H]-PN 200-110 was completely displaced by unla...
Species of differences in postganglionic motor transmission to the retractor penis muscle. 1 Graded motor responses were elicited in isolated, desheathed, thin strips of dog, horse, pig and sheep retractor penis (RP) muscles by field stimulation with trains of 0.2 ms pulses at 10 hertz. These twitches were shown to be neurogenic in all four species, by their prompt extinction in tetrodotoxin.2 alpha-Adrenoceptor blocking drugs abolished the contractile response to noradrenaline and to tyramine in all four species.3 Motor transmission was wholly adrenergic in the horse as in the dog RP because phentolamine rapidly abolished the electrically induced twitches in both these species; but...
The effect of diuretics on the faecal excretion of water and electrolytes in horses. 1. The effect on plasma, urinary and faecal electrolytes of frusemide and hydrochlorthiazide was measured in ponies, mean weight 180 kg. 2. The rapid loss in urine of large quantities of sodium had only a small effect on plasma sodium concentration. 3. Faecal sodium excretion was increased substantially after the administration of frusemide. 4. Frusemide increased faecal potassium during the 48 h following administration and faecal water in the 24/48 h period. It also produced a hypopotassaemia. 5. Hydrochlorthiazide increased faecal chloride during the 24 h after administration. 6. Frusemide ...
Proceedings: Influence of etorphine, acepromazine and diprenorphine on cardiovascular function in ponies. The neuroleptanalgesic drug combination of
etorphine and acepromazine (Large Animal
Immobilon; Reckitt & Colman Ltd.) was
administered i.v. at the recommended dose rate
(24 ,ug/kg etorphine and 100 pg/kg acepromazine)
to twelve Welsh Mountain ponies of 185 to 336 kg
bodyweight. Cardiovascular measurements were
made before and at pre-determined times up to
30 min after the injection. The etorphine
antagonist, diprenorphine (Revivon; Reckitt &
Colman Ltd.), was then injected i.v. (30,ug/kg)
and further measurements were obtained.
Pronounced increases in heart rate, moderate
increase...
Effects of azaperone on cardiovascular and respiratory functions in the horse. 1 The butyrophenone tranquilizer, azaperone, was administered intramuscularly, at dose levels of 0.4 and 0.8 mg/kg, to ponies and its effects on cardiovascular and respiratory functions assessed. 2 Arterial blood pH, CO2 tension (PaCO2) and O2 tension (PaO2) remained relatively constant throughout the course of action of azaperone. 3 Azaperone did not modify plasma protein concentration but venous blood packed cell volume and haemoglobin concentration were reduced by 5 to 10% for at least 4 hours. These changes were probably caused by uptake of erythrocytes into the splenic reservoir. 4 Small ...
The effect of isoprenaline on 86-Rb uptake by horse lymphocytes in vitro. The research studies the effect of a drug called isoprenaline on the intake of a radioactive isotope, 86-Rb, in horse lymphocytes. It finds that isoprenaline has a significant effect increasing […]
Acute systemic anaphylaxis in the horse. 1. Histamine in small doses caused systemic depressor responses in horses, whereas greater doses caused biphasic effects. All doses of 5-hydroxytrypt-amine (5-HT) were pressor and all doses of bradykinin depressor. All three active substances raised pulmonary artery pressure and lowered central venous pressure. 5-HT reduced ventilation volume. Histamine caused brief apnoea followed by hyperpnoea only.2. Acute anaphylaxis in the horse was accompanied by a severe systemic arterial depressor response, a pressor response in the pulmonary artery and vena cava, and alternating phases of apnoea and d...
Influence of halothane and catecholamines on heart rate and rhythm in the horse. 1. Ventricular ectopic beats were recorded in eight of thirteen conscious horses following the intravenous administration of adrenaline in doses of 3 mug/kg. Following pre-treatment with either atropine sulphate (0.1 mg/kg) or propranolol hydrochloride (0.1 mg/kg), the same dose level of adrenaline failed to produce ventricular ectopic beats.2. Halothane anaesthesia sensitized the equine heart to the arrhythmogenic actions of adrenaline; the incidence and duration of ventricular arrhythmias being greater than in conscious animals. In comparison with the findings in conscious horses, ether anae...
The influence of suxamethonium on cardiovascular and respiratory function in the anaesthetized horse. 1. In horses anaesthetized with halothane the intravenous administration of suxamethonium chloride, at a dose level of 0.2 mg/kg, produced a short-lived period of hypoventilation, which was associated with increases in arterial blood PCO(2) levels and in plasma concentrations of bicarbonate, sodium and potassium ions, and reductions in arterial blood pH and PO(2) values.2. The respiratory depressant action of suxamethonium chloride 0.2 mg/kg was accompanied by increases in blood pressure and heart rate. Doses of suxamethonium chloride 0.4 mg/kg produced similar but quantitatively greater chang...