Functional receptors for vasoactive intestinal peptide in cultured vascular smooth muscle cells from rat aorta

Specific binding sites for vasoactive intestinal peptide (VIP), a potent vasodilatory polypeptide, and its effect on formation of intracellular cyclic AMP levels were studied in cultured vascular smooth muscle cells (VSMC) from rat aorta. Specific binding of 125I-labeled-VIP to cultured VSMCs was time- and temperature-dependent. Scatchard analysis of binding studies suggested the presence of two classes of high and low affinity binding sites for VIP; the apparent Kd and the number of maximal binding capacity were approximately 8 X 10(-9) M and 60,000 sites/cell (high-affinity sites) and approximately 4 X 10(-8) M and 140,000 sites/cell (low-affinity sites), respectively. Unlabeled VIP competitively inhibited the binding of 125I-labeled-VIP to its binding sites, whereas neither peptides structurally related to VIP, nor other vasoactive substances affected the binding. VIP stimulated formation of intracellular cyclic AMP in cultured VSMCs in a dose-dependent manner; the stimulatory effect of VIP on cyclic AMP formation was not blocked by propranolol and was additive with isoproterenol. The present study first demonstrates the presence of specific receptors for VIP in VSMCs functionally coupled to adenylate cyclase system. It is suggested that VIP exerts its vasodilatory effect through its specific receptors distinct from beta-adrenergic receptors.