Effect of serotonin on cytosolic free calcium in adrenal glomerulosa and vascular smooth muscle cells.
In view of its vasoconstricting action and of its stimulating effect on aldosterone biosynthesis, serotonin (5-hydroxytryptamine, 5-HT) could play a role in the genesis and/or maintenance of hypertension. The effects are mediated by different specific receptors whose transmembrane signaling system is not elucidated. We have used the fluorescent probe quin 2 to study the effect of 5-HT on cytosolic free calcium in enzymatically dispersed bovine adrenal glomerulosa cells and in cultured rat aortic smooth muscle cells. We also examined the effect of 5-HT on prostacyclin production by rat aortic smooth muscle cells. Serotonin did not modify the level of cytosolic free calcium in adrenal glomerulosa cells. In contrast, serotonin induced rapid, concentration-dependent (10(-8) -10(-5) M) rises of cytosolic free calcium in monolayers of cultured rat aortic smooth muscle cells, from a basal level of 153 +/- 27 nM to peak levels of about 400 nM. Ketanserin (10(-6) M), a specific 5-HT2-receptor antagonist completely blocked the free calcium rise induced by 5-HT. 5-HT induced a concentration-dependent increase in 6-keto-PGF1 alpha production in smooth muscle cells, which was suppressed by ketanserin, indomethacin or removal of calcium from the incubation medium. In contrast nifedipine (10(-6) M) did not modify the response to 5-HT while it abolished the response to vasopressin and did not modify the response to angiotensin II. We conclude that the 5-HT receptors of adrenal glomerulosa cells and vascular smooth muscle cells are linked to two distinct signalling systems which mediate the different biological responses.
Capponi
A M
AM
Division of Endocrinology, University Hospital, Geneva, Switzerland.
Lew
P D
PD
Vallotton
M B
MB
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*
D012701:Serotonin; D015121:6-Ketoprostaglandin F1 alpha; D007650:Ketanserin; D011464:Epoprostenol; D009543:Nifedipine; D002118:Calcium