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W Feniuk

Publications and source records attributed to W Feniuk.

90 records · Page 5Linked to original sources
PubMed1984

5-hydroxytryptamine-induced relaxation of neonatal porcine vena cava in vitro.

5-hydroxytryptamine (5-HT) caused concentration-dependent relaxation of isolated rings from porcine vena cava contracted with alpha-methyl 5-HT or prostaglandin F2 alpha. Relaxation was not blocked by propranolol (1 micron), atropine (1 micron), indomethacin (3 microns), mepyramine (1 micron), cimetidine (1 micron), or cocaine (10 microns). Further receptor analysis could not be performed by antagonism of the relaxant response but was possible using 5-HT induced increases in cyclic AMP. Methysergide (1 micron) but not cyproheptadine (0.1 micron), specifically antagonised the 5-HT induced increase in cyclic AMP with an estimated pA2 of 7.19. The alpha-methyl analogue of 5-HT, a potent agonist at M and D receptors, did not cause relaxation or elevate cyclic AMP. These results suggest that the 5-HT receptor described here is not of the classical M or D type and unlike that described thus far in the vasculature. This receptor shares some similarities with brain 5-HT1 receptors since both may be linked with adenylate cyclase.

1-Methyl-3-isobutylxanthine↗
PubMed1983

5-Hydroxytryptamine-induced relaxation of isolated mammalian smooth muscle.

5-HT caused concentration-dependent relaxation of methoxamine contracted cat isolated saphenous vein and atropine pretreated guinea-pig isolated ileum contracted with histamine. The concentration required to cause 50% of its maximum effect was 7.4 X 10(-7) and 1.4 X 10(-6) mol/l respectively. alpha-Methyl 5-HT was at least 200 times weaker than 5-HT in this respect. The relaxant action of 5-HT in both preparations was not antagonised by atropine, indomethacin, cimetidine, propranolol or tetrodotoxin. In both preparations the relaxant effect was not specifically antagonised by cyproheptadine but was specifically and competitively antagonised by methysergide (pA2 values of 6.75 and 7.37 in cat saphenous vein and guinea-pig ileum, respectively). The results suggest that the 5-HT mediated relaxation in both preparations is mediated directly via a similar 5-HT receptor. The weak antagonistic action of methysergide and lack of relaxant effects with alpha-methyl 5-HT is consistent with the view that this receptor is not a 'D' or 'M' 5-HT-receptor.

Animals↗
PubMed1983

Prejunctional effects of 5-hydroxytryptamine on noradrenergic nerves in the cardiovascular system.

Recent studies indicate that some peripheral noradrenergic nerves have specific 5-hydroxytryptamine (5-HT) receptors on their terminals that can mediate inhibition of release of transmitter after neuronal stimulation. It is now also known that 5-HT will cause norepinephrine release from noradrenergic nerve terminals in the isolated rabbit heart by a receptor mechanism. The evidence for the existence of these two types of prejunctional 5-HT receptor is discussed together with findings to date on their distribution and possible functional importance in the whole animal. In addition 5-HT has weak sympathomimetic actions, which result from its ability to interact with noradrenergic removal processes. The displaced transmitter can then interact with adrenoceptors situated pre- or postjunctionally.

Animals↗
PubMed1981

Modification of the vasomotor actions of methysergide in the femoral arterial bed of the anaesthetized dog by changes in sympathetic nerve activity.

1 Methysergide has been shown to have a remarkably selective vasoconstrictor action in the carotid arterial bed of the anaesthetized dog following intravenous administration. However we have now shown that under conditions which produce sympathetic blockade methysergide will also constrict the femoral arterial bed and the mechanism involved has been investigated. 2 Methysergide (10.100 microgram/kg i.v.) produced small but variable effects on femoral arterial blood flow in the anaesthetized dog. However following ganglion blockade (mecamylamine 5 mg/kg i.v.), section of the lumbar sympathetic chain between L4-L5 or catecholamine depletion with syrosingopine, methysergide consistently caused dose-related decreases in femoral arterial flow which were associated with increases in femoral arterial vascular resistance. 3 Intravenous infusion of methysergide (10 microgram/kg/min) or 5-hydroxytryptamine (5-HT, 10 microgram/kg/min) inhibited the increases in femoral arterial vascular resistance produced by stimulation of the lumbar sympathetic chain by 70% and 44% respectively whilst increases in vascular resistance produced by close intra-arterially administered noradrenaline were potentiated by 25% and 11% respectively 4 Our results show that the vasomotor actions of methysergide in the dog femoral arterial bed are dependent on the degree of sympathetic activity. This suggests that in the dog the post-junctional vasoconstrictor action of methysergide can be masked by a pre-junctional inhibitory effect on sympathetic nerves which may be mediated through stimulation of a specific pre-junctional receptor for 5-HT.

Anesthesia↗
PubMed1981

An analysis of the mechanism of 5-hydroxytryptamine-induced vasopressor responses in ganglion-blocked anaesthetized dogs.

5-Hydroxytryptamine (5-HT) administered intravenously (i.v., 1--30 micrograms kg-1) to ganglion-blocked anaesthetized dogs produced dose-related increases in diastolic blood pressure and we have analysed the mechanism involved. Cyproheptadine and methysergide (10--100 micrograms kg-1 i.v.) were potent and specific antagonists of the 5-HT induced rise in blood pressure, while the alpha-adrenoceptor blocking agent phentolamine (0.3--3 mg kg-1 i.v.) also caused dose-related inhibition. Syrosingopine pretreatment converted the vasopressor action of 5-HT to a vasodepressor action and acute bilateral adrenalectomy caused a marked reduction in the 5-HT-induced rise in blood pressure. In two dogs, 5-HT (30 micrograms kg-1 i.v.) markedly increased the venous plasma concentrations of noradrenaline and adrenaline. We concluded that the 5-HT-induced rise in diastolic pressure in the ganglion blocked anaesthetized dog is due largely to the release of catecholamines of which a substantial component is from the adrenal gland. The rise in diastolic blood pressure is specifically blocked by low doses of cyproheptadine and methysergide suggesting that the release of catecholamines is mediated by specific 5-HT receptors located mainly within the adrenal medulla.

Adrenalectomy↗
PubMed1981

A pre-junctional action of 5-hydroxytryptamine and methysergide on noradrenergic nerves in dog isolated saphenous vein.

Electrical stimulation (2 Hz for 2 min) of dog isolated saphenous vein strips pre-incubated with tritiated noradrenaline increased the overflow of tritium of which about 80% was noradrenaline. 5-Hydroxytryptamine (5-HT; 1.0 x 10-9-1.0 x 10-7 mol litre-1) and methysergide (3.0 x 10-8-3.0 x 10-6 mol litre-1) inhibited the induced overflow of total tritium by a maximum of 78 +/- 4% and 47 +/- 7% respectively (mean +/- s.e. mean, n=6 for each). Methysergide was about 30 times less potent than 5-HT and the maximum inhibition obtained was less than with 5-HT. Both compounds inhibited electrically-induced contractions and overflow of tritiated noradrenaline. Their inhibitory actions on tritium overflow were little affected by phentolamine (1.0 x 10-6 mol litre-1) or cyproheptadine (1.0 x 10-6 mol litre-1), nor was the inhibitory effect of methysergide on electrically induced contractions antagonized by atropine, mepyramine, cimetidine or propranolol. The findings suggest that the prejunctional inhibitory effect of methysergide may be mediated via stimulation of a 5-HT receptor which, unlike the D-receptor, is not blocked by cyproheptadine. The possibility that the pre-junctional 5-HT receptor in the dog saphenous vein is the same as the post-junctional receptor in this preparation is discussed.

Animals↗
PubMed1980

Evidence for two types of excitatory receptor for 5-hydroxytryptamine in dog isolated vasculature.

1 As part of an investigation into the mode of action of anti-migraine drugs, a study of the excitatory receptors for 5-hydroxytryptamine (5-HT) has been carried out in a range of isolated vascular preparations from the dog.2 5-HT contracted the dog isolated femoral artery and saphenous vein over the concentration-range 1.0 x 10(-8) to 5.0 x 10(-6) mol/l.3 In the femoral artery methysergide and cyproheptadine were potent, competitive and specific antagonists of the contractile responses to 5-HT, with pA(2) values of 8.52 and 8.55 respectively.4 In the saphenous vein, methysergide was only a weak antagonist of 5-HT. In addition, it was an agonist over the concentration-range 5.0 x 10(-8) to 1.0 x 10(-5) mol/l. Cyproheptadine was a weak and unsurmountable antagonist of contractile responses to 5-HT and methysergide.5 Contractile responses to 5-HT and methysergide in the saphenous vein were not antagonized by morphine (3.0 x 10(-5) mol/l), indomethacin (5.0 x 10(-5) mol/l), phentolamine (5.0 x 10(-7) mol/l), propranolol (1.0 x 10(-6) mol/l), atropine (1.0 x 10(-6) mol/l), mepyramine (1.0 x 10(-6) mol/l) or cimetidine (1.0 x 10(-5) mol/l).6 In the external carotid and lingual arteries the pattern of activity obtained with methysergide and cyproheptadine was the same as that in the femoral artery, while in the auricular artery the pattern of activity was the same as that in the saphenous vein.7 The results are consistent with the hypothesis that there are two types of receptor mediating 5-HT-induced vasoconstriction in dog vasculature. One type, characterized by the pattern of activity obtained in the femoral artery, is like the previously described ;D-receptor'. The other type, characterized by the pattern of activity obtained in the saphenous vein, has not been described before. The verification of this hypothesis requires the identification of a specific antagonist of 5-HT and methysergide in the saphenous vein.

Animals↗
PubMed1979

Presynaptic inhibitory action of 5-hydroxytryptamine in dog isolated saphenous vein.

1 The effect of 5-hydroxytryptamine on contractile responses to sympathetic nerve stimulation has been studied in the dog isolated saphenous vein.2 Electrical stimulation (0.1 to 10 Hz) of dog saphenous vein strips produced frequency-dependent contractions. Contractions produced by stimulation at 2 Hz were almost completely blocked by tetrodotoxin (3.1 x 10(-8) mol/l) or phentolamine (5.0 x 10(-6) mol/l) but mecamylamine (5.0 x 10(-6) mol/l) had little effect. This suggests that the contractions were mediated predominantly through noradrenaline release from postganglionic noradrenergic nerves.3 Contractions produced by intermittent electrical stimulation at 2 Hz were inhibited by 5-hydroxy-tryptamine (1.0 x 10(-9) to 1.0 x 10(-7) mol/l) in a concentration-dependent manner whilst contractions induced by exogenous noradrenaline were not affected.4 The inhibitory action of 5-hydroxytryptamine was most marked at low frequencies of stimulation and with low pulse numbers.5 High external calcium concentrations (3.9 and 5.2 x 10(-3) mol/l) reduced the inhibitory action of 5-hydroxytryptamine.6 Cyproheptadine (1.0 x 10(-8) mol/l to 1.0 x 10(-6) mol/l) or morphine (1.0 x 10(-7) mol/l to 1.0 x 10(-5) mol/l) did not antagonize the inhibitory action of 5-hydroxytryptamine. Methysergide (1.0 x 10(-7) mol/l) slightly reduced the contractions produced by electrical stimulation and only weakly antagonized the action of 5-hydroxytryptamine.7 It is suggested that a 5-hydroxytryptamine receptor exists presynaptically in the dog isolated saphenous vein strip and that stimulation of this receptor by low concentrations of 5-hydroxytryptamine inhibits the release of noradrenaline from noradrenergic nerves. This receptor type is resistant to blockade by ;classical' 5-hydroxytryptamine antagonists.

Animals↗
PubMed1975

The effects of prostaglandins E1, E2 and F2alpha on vagal bradycardia in the anaesthetized mouse.

1 In anesthetized mice prostaglandins E1 and E2 reduced the bradycardia caused by electrical stimulation of the sectioned peripheral vagus nerve; prostaglandin F2alpha produced only a slight inhibition of the vagal response. 2 None of the prostaglandins studied affected acetylcholine-induced bradycardia. 3 Prostaglandins modify parasympathetic nerve activity in vivo presumably by a pre-synaptic action.

Acetylcholine↗