Pharmacological profile of the receptors that mediate external carotid vasoconstriction by 5‐HT in vagosympathectomized dogs

Carlos M. Villalón, Eduardo Ramírez‐San Juan, Carlos Castillo, Enrique Castillo, Francisco J. López‐Muñoz, José A. Terrón

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    5‐Hydroxytryptamine (5‐HT) can produce vasodilatation or vasoconstriction of the canine external carotid bed depending upon the degree of carotid sympathetic tone. Hence, external carotid vasodilatation to 5‐HT in dogs with intact sympathetic tone is primarily mediated by prejunctional 5‐HT1‐like receptors similar to the 5‐HT1D subtype, which inhibit the carotid sympathetic outflow. The present investigation is devoted to the pharmacological analysis of the receptors mediating external carotid vasoconstriction by 5‐HT in vagosympathectomized dogs. Intracarotid (i.c.) infusions for 1 min of 5‐HT (0.3, 1, 3, 10, 30 and 100 μg) resulted in dose‐dependent decreases in both external carotid blood flow and the corresponding conductance; both mean arterial blood pressure and heart rate remained unchanged during the infusions of 5‐HT. These responses to 5‐HT were resistant to blockade by antagonists at 5‐HT2 (ritanserin) and 5‐HT3/5‐HT4 (tropisetron) receptors, but were partly blocked by the 5‐HT1‐like and 5‐HT2 receptor antagonist, methiothepin (0.3 mg kg−1); higher doses of methiothepin (1 and 3 mg kg−1) caused little, if any, further blockade. These methiothepin (3 mg kg−1)‐resistant responses to 5‐HT were not significantly antagonized by MDL 72222 (0.3 mg kg−1) or tropisetron (3 mg kg−1). The external carotid vasoconstrictor effects of 5‐HT were mimicked by the selective 5‐HT1‐like receptor agonist, sumatriptan (3, 10, 30 and 100 μg during 1 min, i.c.), which produced dose‐dependent decreases in external carotid blood flow and the corresponding conductance; these effects of sumatriptan were dose‐dependently antagonized by methiothepin (0.3, 1 and 3 mg kg‐1), but not by 5‐HT1D‐like receptor blocking doses of metergoline (0.1 mg kg−1). The above vasoconstrictor effects of 5‐HT remained unaltered after administration of phentolamine, propranolol, atropine, hexamethonium, brompheniramine, cimetidine and haloperidol, thus excluding the involvement of α‐ and β‐adrenoceptors, muscarinic, nicotinic, histamine and dopamine receptors. Likewise, inhibition of either 5‐HT‐uptake (with fluoxetine) or cyclo‐oxygenase (with indomethacin), depletion of biogenic amines (with reserpine) or blockade of calcium channels (with verapamil) did not modify the effects of 5‐HT. Taken together, the above results support our contention that the external carotid vasoconstrictor responses to 5‐HT in vagosympathectomized dogs are mainly mediated by activation of sumatriptan‐sensitive 5‐HT1‐like receptors. It must be emphasized, notwithstanding, that other mechanisms of 5‐HT, including an interaction with a novel 5‐HT receptor (sub)type and/or an indirect action that may lead to the release of a known (or even unknown) neurotransmitter substance cannot be categorically excluded. 1995 British Pharmacological Society
    Original languageAmerican English
    Pages (from-to)2778-2784
    Number of pages2499
    JournalBritish Journal of Pharmacology
    StatePublished - 1 Jan 1995


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