Serotonin (5-hydroxytryptamine) (5-HT) is a potent vasoactive amine that reduces renal blood flow and glomerular filtration rate. Vasodilator prostaglandins (PGs) modulate the effects of several vasoconstrictors on the renal circulation. Since mesangial cells are smooth muscle-like cells that may regulate glomerular hemodynamics, we studied the effect of 5-HT on PGs synthesis in rat cultured mesangial cells. 5-HT (10-6-10-3 M) resulted in progressive stimulation of prostaglandin E2 (PGE2) synthesis. Significant stimulation in response to 10-4 M 5-HT started after 2 min of incubation and progressively increased for at least 30 min. This effect was structurally specific for the 5-HT receptor since indole-containing precursors and metabolites of 5-HT as well as the aminergic compounds, adenosine, and dopamine were without effect. Moreover, 5-HT receptor antagonists, but not histaminergic or β-adrenergic antagonists, abolished 5-HT-stimulated PGE2 synthesis. 5-HT also stimulated prostacyclin (measured as 6-ketoprostaglandin F(1α)) but not thromboxane synthesis in the same cell cultures. 5-HT-stimulated PGE2 synthesis was not affected by extracellular calcium depletion but was abolished by preincubating the cells with the intracellular calcium antagonst 8-(N,N-diethylamine)-octyl-3,4-5 trimethoxybenzoate (10-5 M). These studies show that 5-HT stimulates PGE2 and prostacyclin (PGI2) synthesis in mesangial cells via a mechanism dependent on intracellular calcium. These vasodilator PGs may modulate the effect of 5-HT on renal and specifically glomerular hemodynamics.
|Original language||English (US)|
|Journal||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|State||Published - Dec 1 1986|
ASJC Scopus subject areas