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

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 232  (1) , 275-282
Abstract
Somatostatin (SRIF) inhibits stimulated cAMP accumulation and 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 by SRIF of forskolin-stimulated cAMP 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 cAMP synthesis. The inhibition of K+ and 8-bromo-cAMP-stimulated ACTH release by SRIF is attenuated partially by toxin treatment. The ability of forskolin and cholera toxin to stimulate cAMP formation and ACTH release is enhanced by treatment of AtT-20 cells with pertussis toxin. The increased cAMP response to forskolin is prevented by cycloheximide. The data indicate that Ni mediates the inhibition by SRIF of cAMP formation and the ACTH release that results from adenylate cyclase stimulation.