Pertussis toxin treatment blocks the inhibition of somatostatin and increases the stimulation by forskolin of cyclic AMP accumulation and adrenocorticotropin secretion from mouse anterior pituitary tumor cells.
Somatostatin (SRIF) inhibits stimulated cyclic AMP accumulation and adrenocorticotropin (ACTH) release from mouse anterior pituitary tumor cells (AtT-20/D16-16). In order to determine whether guanine nucleotide inhibitory proteins (Ni) mediate these effects, AtT-20 cells were treated with pertussis toxin, an agent that inactivates Ni. Pertussis toxin catalyses the ADP-ribosylation of a 41,000 MW protein in membranes of AtT-20 cells. Pretreatment with pertussis toxin prevents the subsequent ability of toxin to catalyse the labeling of Ni. This effect is dependent on the time of pretreatment and is not reversible. The inhibition of SRIF of forskolin-stimulated cyclic AMP accumulation and ACTH release is prevented by pertussis toxin treatment. The blockade is dependent on the time and concentration of toxin used and is not reversible. Pertussis toxin treatment prevents SRIF from inhibiting corticotropin releasing factor and cholera toxin-stimulated cyclic AMP synthesis. The inhibition of K+ and 8-bromocyclic AMP-stimulated ACTH release by SRIF is attenuated partially by toxin treatment. The ability of forskolin and cholera toxin to stimulate cyclic AMP formation and ACTH release is enhanced by treatment of AtT-20 cells with pertussis toxin. The increased cyclic AMP response to forskolin is prevented by cycloheximide. The data indicate that Ni mediates the inhibition by SRIF of cyclic AMP formation and the ACTH release that results from adenylate cyclase stimulation.
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D004357:Drug Synergism; D019204:GTP-Binding Proteins / Q000494:pharmacology; D051379:Mice; D037342:Pertussis Toxin; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella
D037361:Adenylate Cyclase Toxin; D001427:Bacterial Toxins; D004224:Diterpenes; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D011188:Potassium