Premium
5‐Hydroxytryptamine‐induced tachycardia in the pig: possible involvement of a new type of 5‐hydroxytryptamine receptor
Author(s) -
Bom A.H.,
Duncker D.J.,
Saxena P.R.,
Verdouw P.D.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb10324.x
Subject(s) - ketanserin , methysergide , cyproheptadine , chronotropic , endocrinology , medicine , metergoline , phenoxybenzamine , pharmacology , hexamethonium , receptor , chemistry , muscarinic acetylcholine receptor , 5 ht receptor , serotonin , biology , heart rate , blood pressure
1 The mechanism of 5‐hydroxytryptamine (5‐HT)‐induced tachycardia is species‐dependent and is mediated directly or indirectly either by ‘5‐HT 1 ‐like’ (cat), 5‐HT 2 (rat, dog) or 5‐HT 3 (rabbit) receptors, or by an action similar to tyramine (guinea‐pig). The present investigation is devoted to the analysis of the positive chronotropic effect of 5‐HT in the pentobarbitone‐anaesthetized pig. 2 Intravenous bolus injections of 5‐HT (3, 10 and 30 μg kg −1 ) in pigs resulted in dose‐dependent increases in heart rate of 24 ± 2, 38 ± 3 and 51 ± 3 beats min −1 , respectively ( n = 39). Topical application of a high concentration of 5‐HT (150 μg kg −1 in 5 ml) on the right atrium was also followed by tachycardia (38 ± 6 beats min −1 , n = 4). 3 A number of drugs which antagonize responses mediated by different 5‐HT receptors ‐ phenoxybenzamine, methiothepin, metergoline, methysergide and mesulergine (‘5‐HT 1 ‐like’ and 5‐HT 2 receptors), ketanserin, cyproheptadine, pizotifen and mianserin (5‐HT 2 receptors), and MDL 72222 and ICS 205–930 (5‐HT 3 receptors) — did not attenuate the chronotropic responses to 5‐HT. 4 The 5‐HT‐induced tachycardia was also not affected by antagonists at α‐ and β‐adrenoceptors, muscarinic, nicotinic, histamine and dopamine receptors, and calcium channels. 5 Selective inhibitors of 5‐HT‐uptake, indalpine and fluvoxamine, themselves increased porcine heart rate and facilitated 5‐HT‐induced tachycardia both in magnitude and in duration. 6 A number of putative selective agonists at ‘5‐HT 1 ‐like’ receptors or their possible subtypes (5‐carboxamidotryptamine (5‐CT), 8‐hydroxy‐2‐(di‐N,N‐n‐propylamino) tetralin (8‐OH‐DPAT), BEA 1654 and RU 24969), or at 5‐HT 3 receptors (2‐methyl‐5‐HT), elicited no or only a weak tachycardiac response in the pig. RU 24969, but not 8‐OH‐DPAT, seemed to potentiate the responses to 5‐HT, whereas 5‐CT slightly inhibited these responses. 7 It was concluded that the tachycardia induced by 5‐HT in the pig does not involve the receptors for some common neurotransmitter substances but may be mediated by a new 5‐HT receptor type that is clearly different from ‘5‐HT 1 ‐like’, 5‐HT 2 or 5‐HT 3 receptors.