The specific aims of this proposal are 1) development of radioligand assays using (3H)-arginine8vasopressin in known target tissues for vasopressin including the kidney, vascular smooth muscle, liver and brain, 2) pharmacological characterization of vasopressin binding sites in target tissues, and 3) investigation of the regulation of the vasopressin receptor by homologous hormone using the Brattelboro rat as the model system.

Our working hypothesis is that vasopressin receptor subtypes, analogous to adrenergic receptor subtypes, are present in a tissue specific manner. We base this hypothesis on published data which indicates different second messengers, cyclic AMP and calcium, for vasopressin in kidney and liver, and the development of a series of vasopressin analogues with varying potencies in eliciting vasopressin's actions in target tissues.

We plan to examine binding of (3H)-arginine8vasopressin to membranes prepared from rat renal medulla, isolated hepatocytes, mesenteric artery, hindbrain and septum using techniques already established in my laboratory. Binding sites will be characterized by using commercially available vasopressin analogues and the potencies of these peptides in competing for the binding site will be compared to previously published values for physiological potencies.

The results of studies described in this proposal will be significant in that our understanding of the cellular mechanisms of the action of vasopressin should be increased leading to new clinical strategies for treatment of disorders involving vasopressin.

R01DK034507

1985-04-01

1988-03-31