title: Mechanisms of rapid desensitization to arginine vasopressin in vascular smooth muscle cells.
abstract: 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 less than 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 (less than 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 Gi or Go protein may be involved in some but not all the aspects of the AVP signal transduction and the desensitization phenomena.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Denver 80262.
authors.forename: C
authors.initials: C
authors.lastname: Caramelo
authors.forename: P
authors.initials: P
authors.lastname: Tsai
authors.forename: K
authors.initials: K
authors.lastname: Okada
authors.forename: V A
authors.initials: VA
authors.lastname: Briner
authors.forename: R W
authors.initials: RW
authors.lastname: Schrier
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism / Q000502:physiology; D017483:Receptors, Vasopressin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D010566:Virulence Factors, Bordetella; D001127:Arginine Vasopressin; D037342:Pertussis Toxin; D011493:Protein Kinase C; D002118:Calcium