MECHANISMS OF RAPID DESENSITIZATION TO ARGININE VASOPRESSIN IN VASCULAR SMOOTH-MUSCLE CELLS

This study characterized the rapid desensitization induced by arginine vasopressin (AVP) in vascular smooth muscle cells (VSMC) in culture. The Ca2+ mobilization response and, in some experiments, the intracellular pH changes were used as a probe for the desensitization phenomenon. In VSMC, AVP desensitization was homologous, concentration dependent, and occurred in < 30 s. The desensitization was complete with 10(-7) M AVP. Receptor occupancy was a critical factor in the maintenance of desensitization, since complete hormone washing by acid glycine buffer produced an earlier (< 5 min) recovery of the cell response, whereas partial hormone washing with saline (pH 7.4) required 15 min to produce any significant recovery. Protein kinase C activation was a significant mechanism in AVP desensitization, because protein kinase C downregulation inhibited the desensitization phenomenon. Receptor internalization was, however, not important for the desensitization phenomenon, since it still occurred at 4-degrees-C. Treatment with pertussis toxin did not affect the Ca2+ mobilization response but decreased the AVP-mediated intracellular alkalinization, therefore suggesting that a G(i) or G(o) protein may be involved in some but not all the aspects of the AVP signal transduction and the desensitization phenomena.