External carotid effects of 2-(2-aminoethyl)-quinoline (D-1997) in vagosympathectomized dogs.

Serotonin (5-hydroxytryptamine; 5-HT) elicits external carotid vasoconstriction in vagosympathectomized dogs via 5-HT1B/1D receptors and a mechanism unrelated to the 5-HT1, 5-HT2, 5-HT3 and 5-HT4 types. In order to further explore the nature of this novel mechanism, the canine external 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 sumatriptan to vagosympathectomized dogs dose-dependently decreased external carotid conductance, the rank order of agonist potency being 5-HT > sumatriptan > D-1997. The effects to D-1997 were resistant to intravenous (i.v.) pretreatment with 5-HT2 and 5-HT3/5-HT4 receptor antagonists. Remarkably, the effects induced by lower (10-100 microg/min), but not higher (300-1000 microg/min), doses of D-1997 were blocked by high doses of methiothepin (1 and 3 mg/kg, i.v.), as previously shown with 5-HT. In addition, GR-127935 (1-10 microg/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-adrenoceptors, muscarinic, nicotinic, histamine and dopamine receptors, or inhibition of 5-HT-uptake or cyclo-oxygenase, depletion of biogenic amines or blockade of Ca2+ channels. These results may support our previous contention that lower doses of 5-HT elicit external carotid vasoconstriction in vagosympathectomized dogs by activation of 5-HT1B/1D receptors, whilst higher doses of 5-HT stimulate a novel vasoconstrictor mechanism.