Sumatriptan is an agonist at 5-HT receptors on myenteric neurones in the guinea-pig gastric antrum.
Sumatriptan, a 5-hydroxytryptamine(1D) (5-HT(1D))-receptor agonist used in the treatment in migraine, inhibits gastric motility via the enteric nervous system. As no studies have reported enteric neuronal 5-HT(1D) 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-HT(1P) 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-HT(3) receptor-mediated fast-depolarizing responses or 5-HT(1A) 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-HT(1-7) receptor antagonists. We conclude that sumatriptan behaves as an agonist at the 5-HT(1P) 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.
Tack
J
J
Center for G.I. Research K.U. Leuven, Belgium, University of Leuven, Leuven, Belgium. jan.tack@med.kuleuven.be
Vanden Berghe
P
P
Coulie
B
B
Janssens
J
J
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004594:Electrophysiology; D006168:Guinea Pigs; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D011706:Pyloric Antrum / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1 / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018170:Sumatriptan; C053006:renzapride; D052248:Nitric Oxide Synthase Type I; D002795:Choline O-Acetyltransferase