Stimulation of Aortic Smooth Muscle Prostacyciin by Serotonin: Role of Distinct Receptors in Contractile and Synthetic

It has been shown previously that serotonin stimulates the production of prostacyciin by bovine aortic smooth muscle cells in culture, via 5-HT2 receptors (Coughlin SR, Moskowitz MA, Antoniades HN, Levine L. Proc NatlAcadSci USA 1981;78:7134-7138). These cells express a synthetic phenotype, whereas the majority of the smooth muscle cells in the media from adult arteries are in a contractile state. We have now compared 5-HT stimulated prostacyciin production in bovine aortic media explants, a preparation of contractile smooth muscle, with cultured smooth muscle cells derived from the explants. In the 1-10 fiM range, serotonin stimulates the release of prostacyciin from the explants of bovine aortic media, cultured for a short period. In the presence of cocaine (30 /iM), 1 fiM was sufficient to produce a maximal effect. The stimulatory action of serotonin was sustained with time and did not induce a lasting desensitization. The effect of serotonin on the explants was inhibited only partially (±30%) by ketanserin, a selective and potent 5-HT2 antagonist. It was mimicked by 5-carboxamido-tryptamine, a 5-HT, agonist, but was only weakly inhibited by methiothepin, a 5-HT, antagonist. As expected, in cultured smooth muscle cells, 5-carboxamido-tryptamine was only a weak agonist in stimulating prostacyciin production. In conclusion, it appears that th