EXTERNAL CAROTID EFFECTS OF 2-(2-AMINOETHYL)-QUINOLINE (D-1997) IN VAGOSYMPATHECTOMIZED DOGS

Serotonin (5-hydroxytryptamine; 5-HT) elicits external carotid vasocon striction in vagosympathectomized dogs via 5-HT1B/1D receptors and a m echanism unrelated to the 5-HT1, 5-HT2, 5-HT3 and 5-HT4 types. In orde r to further explore the nature of this novel mechanism, the canine ex ternal carotid effects of 2-(2-aminoethyl)-quinoline (D-1997), a novel 5-HT1 receptor agonist, were analyzed and compared with those of 5-HT and sumatriptan. Intracarotid (i.c.) infusions of 5-HT, D-1997 and su matriptan to vagosympathec tomized dogs dose-dependently decreased ext ernal carotid conductance, the rank order of agonist potency being 5-H T > sumatriptan > D-1997. The effects to D-1997 were resistant to intr avenous (i.v.) pretreatment with 5-HT2 and 5-HT3/5-HT4 receptor antago nists. Remarkably, the effects induced by lower (10-100 mu g/min), but not higher (300-1000 mu g/min), doses of D-1997 were blocked by high doses of methiothepin (1 and 3 mg/kg, i.v.), as previously shown with 5-MT. In addition, GR-127935 (1-10 mu g/kg, i.v.), partially and dose- dependently antagonized D-1997-induced responses. However, the effects of D-1997 remained unaltered after blockade of alpha- and beta-adreno ceptors, muscarinic, nicotinic, histamine and dopamine receptors, or i nhibition of 5-HT-uptake or cyclo-oxygenase, depletion of biogenic ami nes or blockade of Ca2+ channels. These results may support our previo us contention that lower doses of 5-HT elicit external carotid vasocon striction in vagosympathectomized dogs by activation of 5-HT1B/1D rece ptors, whilst higher doses of 5-HT stimulate a novel vasoconstrictor m echanism. (C) 1998 Elsevier Science B.V. All rights reserved.