Premium
Functional characterization of the 5‐HT terminal autoreceptor in the guinea‐pig brain cortex
Author(s) -
Roberts Claire,
Watson; Jeannette,
Burton; Melanie,
Price; Gary W.,
Jones Brian J.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15203.x
Subject(s) - autoreceptor , agonist , 5 ht receptor , medicine , endocrinology , serotonin , guinea pig , antagonist , receptor antagonist , receptor , cerebral cortex , 5 ht1 receptor , partial agonist , biology , chemistry
1 In guinea‐pig cerebral cortical slices in vitro we have shown that the rank order of potency of 5‐hydroxytryptamine (5‐HT), 5‐carboxamidotryptamine and sumatriptan for inhibition of electrically stimulated [ 3 H]‐5‐HT release correlates well with published data on their 5‐HT 1D receptor binding affinites. 2 Both the non‐selective 5‐HT 1D receptor antagonist, methiothepin and the selective 5‐HT 1D receptor antagonist, N‐[4‐methoxy‐3‐(4‐methyl‐1‐piperazinyl]phenyl]‐2′‐methyl‐4′‐(5‐methyl‐1,2,4‐oxadiazole‐3‐yl) [1,1‐biphenyl]4‐carboxamide (GR127935) increased stimulated [ 3 H]‐5‐HT release per se and also attenuated agonist‐induced inhibition of [ 3 H]‐5‐HT release. GR127935 (10nM‐100nM) produced a pA 2 of 9.0 against 5‐HT, which is consistent with its 5‐HT 1D receptor binding affinity. 3 From these findings we conclude that, in guinea‐pig cerebral cortex, the 5‐HT terminal autoreceptor is of the 5‐HT 1D receptor subtype. However, three observations suggest the presence of multiple terminal autoreceptors: shallow inhibition curves to the agonists; a shallow Schild slope of GR127935 antagonism and differences in the maximal responses to 5‐HT between whole cortex and frontal cortex.