Unravelling the pharmacological profile of the canine external carotid vasodilator '5-HT1-like" receptors: coexistence of sympatho-inhibitory 5-HT1B and postjunctional 5-HT7 receptors

It has been suggested that the external carotid vasodilatation produced by serotonin (5-hydroxytryptamine; 5-HT) in anaesthetised dogs with intact vag osympathetic trunks is mediated by sympatho-inhibitory '5-HT1D' receptors a nd musculotropic '5-HT1-like' receptors. The present study has re-analysed this suggestion with regard to the classification schemes recently proposed by the NC-IUPHAR subcommittee on 5-HT receptors. In pentobarbital-anaesthe tised dogs with intact vagosympathetic trunks, 1-min intracarotid (i.c.) in fusions of 5-carboxamidotryptamine (5-CT; 0.01-0.3 mug/min), 5-HT (0.3-30 m ug/min), 5-methoxytryptamine (5-MeO-T; 1-100 mug/min) or sumatriptan (1-100 mug/min) dose-dependently increased the external carotid blood flow withou t affecting blood pressure or heart rate. The selective 5-HT1D receptor ago nist, PNU-142633 (1-1000 mug/min), was essentially inactive. After mesulerg ine (300 mug/kg, i.v.), an antagonist at cardiovascular 5-HT7 receptors, th e above responses to 5-HT, 5-CT and 5-MeO-T were blocked, whilst those to s umatriptan remained unaffected. In contrast, after the 5-HT1B/1D receptor a ntagonist, GR127935 (10 mug/kg, i.v.), the responses to 5-MT, 5-CT and 5-Me O-T were not affected, but those to sumatriptan were abolished. Furthermore , after the selective 5-HT1B receptor antagonist, SB224289 (300 mug/kg, i.v .), the responses to 5-MT, 5-CT and 5-MeO-T were significantly enhanced, wh ereas those to sumatriptan were abolished. Interestingly, the responses to all these agonists remained unmodified after the selective 5-HT1D receptor antagonist, BRL15572 (300 mug/kg, i.v.). The above results suggest that the '5-HT1-like' receptors, which mediate canine external carotid vasodilatati on, display the pharmacological profile of sympatho-inhibitory 5-HT1B recep tors and musculotropic 5-HT7 receptors, and confirm the existence of vasoco nstrictor 5-HT1B receptors.