FURTHER CHARACTERIZATION OF THE 5-HYDROXYTRYPTAMINE(1)-LIKE RECEPTORS MEDIATING THE INCREASE IN EXTERNAL CAROTID BLOOD-FLOW IN THE DOG

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-HT1-like receptors. In the present investigation, we have further characterized these 5-HT1-like receptors. Like 5-HT, 1 min intracarotid (i.c.) infusions of the 5-HT1A 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-HT1A receptor agonists, 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT), buspirone and ipsapirone, or the 5-HT1A/5-HT1B 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-HT1C/5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl-)-aminopropane (DOI) and the 5-HT3 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-HT1C and 5-HT2 receptor antagonist, ritanserin, but was potently antagonized by the mixed 5-HT1-like and 5-HT2 receptor antagonist, methiothepin, or completely abolished after sympathectomy. Unlike methiothepin, the 5-HT1A and 5-HT1B 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-HT1-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-HT1A, 5-HT1B, or 5-HT1C binding sites. (C) 1993 Wiley-Liss, Inc.