title: Na(+)-dependent metabolic coupling upon 5-HT1B receptor activation by sumatriptan and related agonists.
abstract: The efficacy of the antimigraine compound sumatriptan in migraine relief has been attributed to its interaction with 5-HT1B receptors in cerebral blood vessels causing cranial vasoconstriction, and/or on nerve endings of the trigeminovascular system in the dura mater inhibiting the inflammatory process by decreasing neuropeptide release. Otherwise, the metabolic effects following 5-HT1B receptor activation are largely unknown. In CHO-K1 cells expressing recombinant h5-HT1B receptors, activation of these receptors by sumatriptan and related agonists enhanced their metabolic rate by 34.9%, but not in wild-type cells. Treatment with pertussis toxin (100 ng/ml), addition of the 5-HT1B receptor antagonist GR127935 (30 nM), attenuation or substitution of the extracellular glucose supply, prevented the sumatriptan-mediated enhancement of the metabolic rate. This metabolic enhancement was also blocked by washout of extracellular Na+, independent of the blockade of the Na+/H+ antiporter by ethylisopropylamiloride. The Na(+)-dependent metabolic enhancement by sumatriptan suggests activated 5-HT1B receptors pilot cellular energy demand. This metabolic feature may contribute to the mode of action of 5-HT1B agonists in migraine relief.
authors.affiliation: Centre de Recherche Pierre Fabre, Department of Cellular and Molecular Biology, Castres, France. crpfl@starway.tm.fr.pauwels
authors.forename: P J
authors.initials: PJ
authors.lastname: Pauwels
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism*; D018170:Sumatriptan / Q000378:metabolism / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology
chemical_list: D010069:Oxadiazoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; C090701:GR 127935; D018170:Sumatriptan; D012964:Sodium