OPERATIONAL CHARACTERISTICS OF THE 5-HT1-LIKE RECEPTORS MEDIATING EXTERNAL CAROTID VASOCONSTRICTION IN VAGOSYMPATHECTOMIZED DOGS - CLOSE RESEMBLANCE TO THE 5-HT1D RECEPTOR SUBTYPE

It has recently been shown that the external carotid vasoconstrictor r esponse to 5-HT in the dog is primarily mediated by sumatriptan-sensit ive 5-HT1-like receptors; however, the fact that these receptors are n ot blocked by metergoline, a 5-HT1D ligand, raises questions about the ir possible correlation with the 5-HT1D receptor subtype. Since a numb er of drugs display high affinity for the 5HT(1D) (GR127935)and 5-HT1F (e.g. methysergide and oxymetazoline) receptor subtypes, in this stud y we have used these drugs to determine whether the above vasoconstric tor 5-HT1-like receptors correlate with the 5-HT1D and/or 5-HT1F recep tor subtypes. One-minute intracarotid infusions of 5-HT (0.3-30 mu g/m in), sumatriptan (1-30 mu g/min), oxymetazoline (0.03-3 mu g/min) and noradrenaline (0.3-3 mu g/min) resulted in dose-dependent decreases in external carotid blood flow without changes in arterial blood pressur e or heart rate. These vasoconstrictor responses remained unaltered af ter i.v. administration of physiological saline (0.015, 0.05 and 0.15 ml/kg; n = 4) or ritanserin (1 mg/kg; n = 5). In contrast, GR127935 (1 , 3 and 10 mu g/kg, n = 6) potently blocked the responses to 5-HT (unm asking a dose-dependent vasodilator component) and sumatriptan without affecting those to oxymetazoline or noradrenaline. Interestingly, met hysergide (10, 30 and 100 mu g/kg, n = 5) also blocked the vasoconstri ctor responses to 5-HT and sumatriptan, but unlike GR127935, did not r evert the vasoconstrictor response to 5-HT; the responses to oxymetazo line remained unaffected, but those to noradrenaline were apparently a ttenuated by the highest dose. Taken together, the above findings sugg est that the sumatriptan-sensitive 5-HT1-like receptors mediating cani ne external carotid vasoconstriction resemble 5-HT1D receptors, probab ly of the 5-HT1D beta subtype on the basis of the resistance to blocka de by ritanserin. The pharmacological profile of these receptors could be similar (bovine and human cerebral arteries, porcine carotid arter iovenous anastomoses and human coronary arteries) to other putative 5- HT1D receptors mediating vascular responses.