Serotonin (5-HT) stimulates prostacyclin (PGI2) production by bovine aortic smooth muscle cells in culture via 5-HT2 receptors (1). These cells express a synthetic phenotype (2), whereas the majority of the smooth muscle cells in the media from adult arteries are in a contractile state. We have now shown that 5-HT (1-10 μM) also stimulates PGI2 production by a preparation of contractile smooth muscle cells : explants from bovine aortic media cultured for short periods. This effect is independent from 5-HT2 receptors : it is only partially inhibited (±30%) by ketan-serin (a selective and potent 5-HT2 antagonist) and is perfectly mimicked by a 5-HT1 agonist, 5-carboxamidotryptamine. 5-HT2 receptors seem to be linked to a phospholipase C (3), with subsequent accumulation of inositol tr isphosphate , Ins(1,4,5)P3, and diacylglycerol, an activator of protein kinase C. We have observed a stimulatory effect of phorbol 12-myristate, 13-acetate (a selective activator of kinase C) on PGI2 production by the bovine aortic smooth muscle cells (synthetic state), whereas it was totally ineffective on media explants preparation (contractile state). Furthermore, in the smooth muscle cells in culture, the 5-HT effect can be inhibited by (ethyl-isopropyl)amiloride, a potent and selective inhibitor of the Na+/H+ antiporter. In conclusion it appears that the regulation mechanisms of PGI2 production in arterial smooth muscle cells are strongly dependent an the phenotypic state of these cells. The control of PGI2 release via 5-HT2 receptors seems to involve a cytoplasmic alkalinization, via the activation of protein kinase C. The mechanism of 5-HT action in the media explants remains to be elucidated.(1) Coughlin, S.R. et al.: Proc . Natl. Acad. Sci. USA 78(11), 7134-7138, 1981.(2) Chamley-Campbell, J.H. and Campbell, G.K.: Atherosclerosis 40, 347-357, 1981.(3) Roth, B.L. et al.: J. Pharm. Exp. Ther. 238(2), 480-485, 1986.
Protein kinase C is involved in the cyclooxygenase-2 expression in rat aortic smooth muscle cells