Inhibition of formation of cyclic AMP and cyclic GMP by vasopressin in smooth-muscle cells is insensitive to pertussis toxin.
Pretreatment of A-10 cells with pertussis toxin had no effect on [arginine]vasopressin-mediated inhibition of cyclic nucleotide accumulation. Pretreatment of the cells with the same concentration of pertussis toxin produced 90-95% inhibition of [32P]ADP ribosylation in membranes, suggesting that these cells possess pertussis-toxin substrate and that the toxin enters the cells to reach its site of action. The functional integrity of the pertussis-toxin substrate in these cells is confirmed by the observation that in these cell membranes increasing concentrations of GTP inhibited basal, forskolin- and NaF-stimulated adenylate cyclase activities, and this inhibition was abolished when the cells were pretreated with pertussis toxin. In addition, thrombin-mediated inhibition of isoprenaline-stimulated cyclic AMP accumulation was also inhibited by pertussis-toxin pretreatment of the cells. These data suggest that, unlike thrombin, [arginine]vasopressin-induced inhibitory effects on cyclic nucleotide accumulation in smooth-muscle cells are not mediated by pertussis-toxin substrate.
Nambi
P
P
Department of Molecular Pharmacology, SK&F Laboratories, Philadelphia, PA 19101.
Whitman
M
M
Aiyar
N
N
Crooke
S T
ST
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis*; D006152:Cyclic GMP / Q000096:biosynthesis*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006160:Guanosine Triphosphate / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D051381:Rats; D013917:Thrombin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D010566:Virulence Factors, Bordetella; D001127:Arginine Vasopressin; D000246:Adenosine Diphosphate Ribose; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D013917:Thrombin; D006152:Cyclic GMP