title: Metitepine distinguishes two receptors mediating inhibition of [3H]-5-hydroxytryptamine release in guinea pig hippocampus.
abstract: Inhibition of [3H]-5-hydroxytryptamine ([3H]-5-HT) release from guinea pig brain slices via activation of the terminal 5-HT autoreceptor has previously been characterised as a model of 5-HT1D receptor activation, based on the rank potencies of a range of agonists, and the potent antagonism of the inhibitory effects of 5-HT by metitepine. The present study uses this model, in slices of the guinea pig hippocampus, to examine the antagonist potency of metitepine against the 5-HT receptor agonists sumatriptan, 5-carboxamidotryptamine (5-CT) and 5-HT. Addition of metitepine to the perfusion buffer (30, 300 and 1000 nmol/l) significantly shifted the concentration-response curve to 5-HT, producing a Schild slope of 1.1, and a pA2 value of 7.6. However, the ability of metitepine to antagonise the effects of sumatriptan or 5-CT in this model was less marked. A clear-cut shift in the concentration-response curve to sumatriptan was only achieved at 1000 nmol/l metitepine (apparent pA2 = 6.7), and this was similar to the ability of metitepine to attenuate the effects of 5-CT (apparent pA2 7.0 at 300 nmol/l and 6.7 at 1000 nmol/l). These findings suggest heterogeneity in the receptor mediating inhibition of [3H]-5-HT release in guinea pig hippocampus.
authors.affiliation: Merck, Sharp and Dohme, Neuroscience Research Centre, Harlow, Essex, UK.
authors.forename: L O
authors.initials: LO
authors.lastname: Wilkinson
authors.forename: D N
authors.initials: DN
authors.lastname: Middlemiss
mesh_terms: D000818:Animals; D046508:Culture Techniques; D004558:Electric Stimulation; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D018170:Sumatriptan
chemical_list: D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D012701:Serotonin; D008719:Methiothepin; D018170:Sumatriptan; C047087:5-carboxamidotryptamine