NA-DEPENDENT METABOLIC COUPLING UPON 5-HT1B RECEPTOR ACTIVATION BY SUMATRIPTAN AND RELATED AGONISTS()

The efficacy of the antimigraine compound sumatriptan in migraine reli ef has been attributed to its interaction with 5-HT1B receptors in cer ebral blood vessels causing cranial vasoconstriction, and/or on nerve endings of the trigeminovascular system in the dura mater inhibiting t he inflammatory process by decreasing neuropeptide release. Otherwise, the metabolic effects following 5-HT1B receptor activation are largel y unknown. In CHO-K1 cells expressing recombinant h5-HT1B receptors, a ctivation of these receptors by sumatriptan and related agonists enhan ced their metabolic rate by 34.9%, but not in wild-type cells. Treatme nt with pertussis toxin (100 ng/ml), addition of the 5-HT1B receptor a ntagonist GR127935 (30 nM), attenuation or substitution of the extrace llular 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 e nhancement by sumatriptan suggests activated 5-HT1B receptors pilot ce llular energy demand. This metabolic feature may contribute to the mod e of action of 5-HT1B agonists in migraine relief.