ROLE OF 5-HT(1)-LIKE RECEPTORS IN THE INCREASE IN EXTERNAL CAROTID BLOOD-FLOW INDUCED BY 5-HYDROXYTRYPTAMINE IN THE DOG

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 mug) and 5-carboxamidotryptamine (5-CT; 0.01, 0.03, 0.1 and 0.3 mug) 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-HT, receptor antagonist, ritanserin (100 mug/kg i.v.), nor the 5-HT3 receptor antagonist, 1alphaH,3alpha,5alphaH-tropan-3yl-3,5-dichlorobenzoate (MDL 72222; 140 mug/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 mug/kg i.v.). Interestingly, the 5-HT1A and 5-HT1B receptor antagonist, cyanopindolol (100, 300 and 1000 mug/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 mug/min 5-CT being significantly antagonized by the highest dose of cyanopindolol; however, this blockade was not selective. Unlike 5-HT and 5-Cr, 1 min i.c. infusions of either the 5-HT1C/5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (DOI; 30-300 mug), or the 5-HT3 receptor agonist, 2-methyl-5-HT (10-300 mug), 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.