HETEROTRIMERIC G-PROTEIN CANDIDATES FOR GE IN THE ACTH SECRETORY PATHWAY

The mouse AtT-20/D16-16 anterior pituitary tumour cell line was used t o identify candidate heterotrimeric G-proteins for G-exocytosis (G(e)) which mediates calcium ion-stimulated adrenocorticotrophin (ACTH) sec retion in this cell line. AtT-20 cells express several heterotrimeric G-protein a subunits; G(s alpha), G(t alpha), G(q alpha), G(11 alpha), G(12 alpha), G(13 alpha), G(14 alpha), G(15 alpha), G(z alpha,), G(i2 alpha) G(i3 alpha) and G(o alpha) and so heterotrimeric G-protein sel ective agents were used to differentiate between these candidates. Age nts which stimulate ACTH secretion via G(e) were not pertussis toxin ( PTX)-sensitive nor was cholera toxin (CTX) able to stimulate ACTH secr etion from permeabilised cells in the absence of calcium. G-protein an tagonists which inhibit activation of G(s), G(i), and G(q) subfamilies did not attenuate G(e)-stimulated ACTH secretion from permeabilised A tT-20 cells. In AtT-20 cells the stimulatory G-protein involved in the late stages of the ACTH secretory pathway does not belong to the G(s) , G(i) (with the exception of G(z)) or G(q) subfamilies of heterotrime ric G-proteins leaving G(z), G(12) or G(13) as the strongest candidate s for G(e). (C) 1998 Elsevier Science Ireland Ltd. All rights reserved .