Sumatriptan is an agonist at 5-HT1P receptors on myenteric neurones in the guinea-pig gastric antrum


Jan Tack MD, PhD, Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
Tel: +32 16 34 42 25; fax: +32 16 34 44 19;


Abstract  Sumatriptan, a 5-hydroxytryptamine1D (5-HT1D)-receptor agonist used in the treatment in migraine, inhibits gastric motility via the enteric nervous system. As no studies have reported enteric neuronal 5-HT1D receptors, we used conventional intracellular recordings to characterize the actions of sumatriptan on 145 guinea-pig antral myenteric neurones. In 24 of 29 neurones with a 5-HT1P receptor-mediated depolarizing response to 5-HT, application of sumatriptan caused a dose-dependent depolarization, accompanied by increased membrane resistance and enhanced excitability. Depolarizing responses to sumatriptan occurred both in cholinergic and in nitrergic neurones. Sumatriptan did not mimic the 5-HT3 receptor-mediated fast-depolarizing responses or 5-HT1A receptor-mediated inhibitory responses to 5-HT. Sumatriptan had no effect on neurones not responding to 5-HT. The depolarizing response to sumatriptan was inhibited by renzapride, but not by 5-HT1−7 receptor antagonists. We conclude that sumatriptan behaves as an agonist at the 5-HT1P receptor on myenteric neurones in the guinea-pig gastric antrum. The actions of sumatriptan on gastric motility seem to be attributable to a direct action on enteric neurones.