Further evidence that the serotonin receptor in the rat stomach fundus is not 5HT 1A or 5HT 1B

Abstract

The nature of the receptor mediating serotonin contraction in the rat stomach fundus has not been clearly associated with either 5HT 1 or 5HT 2 receptors. We have explored the possibility that such receptors in the rat fundus may better correlate with 5HT 1A or 5HT 1B receptor subtypes as defined by radiolabeled ligand binding studies with brain cortical membranes. Meta chlorophenylpiperazine (CPP) and meta trifluoromethylphenylpiperazine (TFMPP), selective ligands for the 5HT 1B receptor and LY165163, a selective ligand for the 5HT 1A receptor, have been evaluated for their agonist and antagonist activity at serotonin receptors in the rat stomach fundus. CPP and TFMPP were partial agonists in the rat stomach fundus whereas LY165163 showed no agonist activity in this smooth muscle in concentrations up to 10 −4M. All three phenylpiperazines antagonized serotonin-induced contractions in the rat stomach fundus. The affinity for serotonin receptors in the rat fundus was similar for all three phenylpiperazines in spite of the reported selectivity of MCPP and TFMPP for 5HT 1B and of LY165163 for 5HT 1A receptors. Furthermore, the affinity of these agents for serotonin receptors in the rat stomach fundus did not agree with their reported affinity for either 5HT 1A or 5HT 1B binding sites in rat cortical membranes. Thus, the similarity in affinities of these phenylpiperazine derivatives for serotonin receptors mediating contraction in the rat fundus along with their different affinities for 5HT 1A and 5HT 1B binding sites argues against the possibility that the serotonin receptor in the rat fundus is of the 5HT 1A or 5HT 1B subtype of serotonin receptor.