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Further characterization of the 5‐hydroxytryptamine 1 ‐like receptors mediating the increase in external carotid blood flow in the dog
Author(s) -
Villaón Carlos M.,
Terrón José A.,
Hong Enrique
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430290404
Subject(s) - ritanserin , agonist , ipsapirone , pindolol , endocrinology , medicine , 5 ht receptor , receptor antagonist , chemistry , receptor , partial agonist , methysergide , ketanserin , pharmacology , antagonist , buspirone , serotonin , biology
It has recently been shown that the increase in external carotid blood flow (external CBF) produced by 5‐hydroxytryptamine (5‐HT) in the anaesthetized dog, being mimicked by 5‐carboxamidotryptamine, potently blocked by methiothepin and resistant to blockade by ritanserin and MDL 72222, is mediated by 5‐HT 1 ‐like receptors. In the present investigation, we have further characterized these 5‐HT 1 ‐like receptors. Like 5‐HT, 1 min intracarotid (i.c.) infusions of the 5‐HT 1A receptor agonist, indorenate, produced an increase in external CBF without modifying mean arterial blood pressure or heart rate. Contrasting with indorenate, 1 min i.c. infusions of the 5‐HT 1A receptor agonists, 8‐hydroxy‐2(di‐N‐propylamino)tetralin (8‐OH‐DPAT), buspirone and ipsapirone, or the 5‐HT 1A /5‐HT 1B receptor agonist, 5‐methoxy‐3‐[1,2,3,6‐tetrahydro‐4‐pyridinyl]‐1‐H‐indol succinate (RU 24969), resulted in dose‐dependent decreases in external CBF; furthermore, both the 5‐HT 1C /5‐HT 2 receptor agonist, 1‐(2,5‐dimethoxy‐4‐iodophenyl‐)‐aminopropane (DOI) and the 5‐HT 3 receptor agonist, 2‐methyl‐5‐hydroxytryptamine (2‐methyl‐5‐HT), were essentially inactive. Thus, only indorenate increased the external CBF in the dog; this effect of indorenate was not antagonized by intravenous (i.v.) administration of the 5‐HT 1 and 5‐HT 2 receptor antagonist, methiothepin, or completely abolished after sympathectomy. Unlike methiothepin, the 5‐HT 1A and 5‐HT 1B receptor antagonist, (±)‐pindolol, did not block indorenate‐induced external carotid vasodilatation. Together, the above results support the notion that indorenate is acting on the 5‐HT 1 ‐like receptors involved in the increase in external CBF in the dog. These receptors, which are probably located on carotid sympathetic nerve endings, do not seem to correspond to either the 5‐HT 1A , 5‐HT 1B , or 5‐HT 1C binding sites. © 1993 Wiley‐Liss, Inc.