Effects of Vasopressin and Its Analogs on Rat Aortic Smooth Muscle and Renal Medullary Tubular Cells

Abstract

The response to activation of specific receptors by arginine-vasopressin (AVP) has been studied in two cell models. In rat aortic smooth muscle cells in monolayer culture, the response of cytosolic free calcium ([Ca2+]i) upon addition of various agonists or antagonists was examined using the fluorescent calcium probe Quin 2. Activation of the vasopressin (V1) subtype of receptor resulted in a transient rise of [Ca2+]i, which could be prevented by a selective V1 antagonist but not by the calcium channel blocker, nifedipine and that was only slightly reduced in the absence of calcium in the medium. Release of 6-keto-prostaglandin F1 alpha (PGF1 alpha), a stable metabolite of prostacyclin, was also observed in response to AVP. We conclude that one of the primary intracellular events following activation of V1 receptors on smooth muscle cells is a rise of [Ca2+]i released from intracellular stores, which mediates smooth muscle contraction and prostacyclin production. In superfused rat renal medullary tubular cells, the study of the release of cyclic AMP (cAMP) and prostaglandin E2 (PGE2) upon stimulation by AVP and various analogs (agonists or antagonists) permitted demonstration of the presence of two subtypes of receptors. The V2 type appeared to be linked to adenylate cyclase and was responsible for cAMP release, mediating the hydroosmotic effect of AVP, whereas the V1 type was related to calcium, mediating the prostaglandin production.