title: Role of 5-HT1-like receptors in the increase in external carotid blood flow induced by 5-hydroxytryptamine in the dog.
abstract: This study investigated the receptor involved in the 5-hydroxytryptamine (5-HT)-induced increase in external carotid blood flow in pentobarbital-anaesthetized dogs. One-minute intracarotid (i.c.) infusions of 5-HT (0.3, 1, 3 and 10 micrograms) and 5-carboxamidotryptamine (5-CT; 0.01, 0.03, 0.1 and 0.3 micrograms) produced dose-dependent increases in external carotid blood flow without changes in mean arterial blood pressure or heart rate. After vagosympathectomy, the above vasodilator responses to 5-HT and 5-CT were abolished and remained so even after restoration of carotid vascular tone with noradrenaline. Furthermore, the 5-HT- and 5-CT-induced increases in external carotid blood flow were not modified by the 5-HT2 receptor antagonist, ritanserin (100 micrograms/kg i.v.), nor the 5-HT3 receptor antagonist, 1 alpha H,3 alpha, 5 alpha H-tropan-3yl-3,5-dichlorobenzoate (MDL 72222; 140 micrograms/kg i.v.), but were potently and dose dependently antagonized by the mixed 5-HT1-like and 5-HT2 receptor blocker, methiothepin (3, 10 and 30 micrograms/kg i.v.). Interestingly, the 5-HT1A and 5-HT1B receptor antagonist, cyanopindolol (100, 300 and 1000 micrograms/kg i.v.), blocked the effects of 5-HT, but the block was not elicited in a dose-dependent manner, with only the response induced by 0.3 microgram/min 5-CT being significantly antagonized by the highest dose of cyanopindolol; however, this blockade was not selective. Unlike 5-HT and 5-CT, 1 min i.c. infusions of either the 5-HT1C/5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (DOI; 30-300 micrograms), or the 5-HT3 receptor agonist, 2-methyl-5-HT (10-300 micrograms), were devoid of effects on the canine external carotid blood flow. It is concluded that the 5-HT-induced increase in external carotid blood flow is mediated by 5-HT1-like receptors probably located on carotid sympathetic nerves. These receptors, however, do not seem to correspond to either the 5-HT1A, 5-HT1B or 5-HT1C receptor subtypes.
authors.affiliation: Departamento de Farmacología y Toxicología, CINVESTAV, I.P.N., México D.F., Mexico.
authors.forename: C M
authors.initials: CM
authors.lastname: Villalón
authors.forename: J A
authors.initials: JA
authors.lastname: Terrón
authors.forename: E
authors.initials: E
authors.lastname: Hong
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002342:Carotid Artery, External / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology; D011985:Receptors, Serotonin / Q000032:analysis / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology
chemical_list: D011976:Receptors, Muscarinic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; C047087:5-carboxamidotryptamine; D000109:Acetylcholine; D009638:Norepinephrine