Serotonin receptor activation of phosphoinositide turnover in uterine, fundal, vascular, and tracheal smooth muscle.

Hydrolysis of phosphatidylinositol is becoming recognized as the second messenger system for a number of hormones and neurotransmitters, including serotonin. The present study was designed to explore the effects of serotonin to enhance phosphoinositide turnover in several smooth muscle preparations, in an effort (a) to determine which smooth muscle preparation might provide a useful system for further study of phosphoinositide turnover and (b) to examine the role of 5-HT2 receptors in such responses. Basal-[3H]inositol monophosphate ([3H]IP) formation was 10-fold higher in the uterus than in the rat jugular vein, aorta, stomach fundus, or guinea pig trachea.

2,3-Dialkyl(dimethylamino)indoles: interaction with 5HT1, 5HT2, and rat stomach fundal serotonin receptors.

2,3-Dialkyl(dimethylamino)indoles, synthesized via the Fisher indole synthesis, were found to weakly bind to 5HT1 and 5HT2 sites in brain cortical membranes (IC50 greater than 1 microM at both sites for all compounds). These (dimethylamino)indoles were relatively potent antagonists of the serotonin receptor in the rat stomach fundus. At higher concentrations, several of the compounds were weak agonists at this receptor.

Effect of nitrendipine, diltiazem, trifluoperazine and pimozide on serotonin2 (5-HT2) receptor activation in the rat uterus and jugular vein.

The present study explored the calcium source used in serotonin (5-HT)-induced contractions mediated by 5-HT2 receptor activation in the rat uterus and jugular vein in vitro. In the rat uterus, the calcium channel antagonists, nitrendipine and diltiazem, and the neuroleptic agents, trifluoperazine (TFP) and pimozide, antagonized potently and noncompetitively 5-HT-induced contractions. These data are compatible with the contention that 5-HT-induced contractions in uterine smooth muscle require extracellular sources of calcium.

Localization of a felodipine (dihydropyridine) binding site on calmodulin.

The fluorescent dihydropyridine calcium antagonist drug felodipine binds to calmodulin (CaM) in a Ca2+-dependent manner. Its binding can be regulated by the interaction of CaM antagonist drugs through allosteric mechanisms [Mills, J.S.

Further evidence that the serotonin receptor in the rat stomach fundus is not 5HT1A or 5HT1B.

The nature of the receptor mediating serotonin contraction in the rat stomach fundus has not been clearly associated with either 5HT1 or 5HT2 receptors. We have explored the possibility that such receptors in the rat fundus may better correlate with 5HT1A or 5HT1B receptor subtypes as defined by radiolabeled ligand binding studies with brain cortical membranes. Meta chlorophenylpiperazine (CPP) and meta trifluoromethylphenylpiperazine (TFMPP), selective ligands for the 5HT1B receptor and LY165163, a selective ligand for the 5HT1A receptor, have been evaluated for their agonist and antagonist activity at serotonin receptors in the rat stomach fundus.