Subclassification of presynaptic 5-HT autoreceptors in the human cerebral cortex as 5-HT1D receptors.
Human cerebral cortical synaptosomes were used to determine the 5-hydroxytryptamine (5-HT) receptor subtype to which the inhibitory presynaptic 5-HT autoreceptor belongs. The synaptosomes preincubated with [3H]5-HT were superfused and tritium overflow was stimulated by high K+. The K(+)-evoked tritium overflow, which was Ca(2+)-dependent but tetrodotoxin-resistant, was concentration-dependently inhibited by the nonselective 5-HT 1D alpha/1D beta receptor agonist, 5-carboxamidotryptamine. Ketanserin at a concentration which should block the 5-HT 1D alpha but not the 5-HT 1D beta receptor failed to antagonize the inhibitory effect of 5-carboxamidotryptamine. In contrast, the nonselective 5-HT 1D alpha/1D beta receptor antagonist, methiothepin, at a concentration which should block both the 5-HT 1D alpha and the 5-HT 1D beta receptor abolished the effect of 5-carboxamidotryptamine. It is concluded that the presynaptic 5-HT autoreceptor, which has previously been classified as 5-HT 1D, belongs to the 5-HT1D beta subtype.
Fink
K
K
Institut für Pharmakologie und Toxikologie, Universität Bonn, Germany.
Zentner
J
J
Göthert
M
M
D000328:Adult; D017660:Autoreceptors / Q000145:classification*; D002540:Cerebral Cortex / Q000737:chemistry*; D005260:Female; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D017661:Receptors, Presynaptic / Q000145:classification*; D011985:Receptors, Serotonin / Q000145:classification*; D012701:Serotonin / Q000378:metabolism
D017660:Autoreceptors; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D012701:Serotonin; D007650:Ketanserin