AJP - Renal Physiology, Vol 251, Issue 5 844-F850, Copyright © 1986 by American Physiological Society
Effect of serotonin on prostaglandin synthesis in rat cultured mesangial cells
T. Knauss and H. E. Abboud
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 beta-adrenergic antagonists,
abolished 5-HT-stimulated PGE2 synthesis. 5-HT also stimulated prostacyclin
(measured as 6-ketoprostaglandin F1 alpha) 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 antagonist
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.
