Heterotrimeric G-protein candidates for Ge in the ACTH secretory pathway.

ABSTRACT

The mouse AtT-20/D16-16 anterior pituitary tumour cell line was used to identify candidate heterotrimeric G-proteins for G-exocytosis (Ge) which mediates calcium ion-stimulated adrenocorticotrophin (ACTH) secretion in this cell line. AtT-20 cells express several heterotrimeric G-protein alpha subunits; Gs alpha, Gt alpha, Gq alpha, G11alpha, G12alpha, G13alpha, G14alpha, G15alpha, Gz alpha, Gi2alpha, Gi3alpha, and Go alpha and so heterotrimeric G-protein selective agents were used to differentiate between these candidates. Agents which stimulate ACTH secretion via Ge were not pertussis toxin (PTX)-sensitive nor was cholera toxin (CTX) able to stimulate ACTH secretion from permeabilised cells in the absence of calcium. G-protein antagonists which inhibit activation of Gs, Gi, and Gq subfamilies did not attenuate Ge-stimulated ACTH secretion from permeabilised AtT-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 Gs, Gi (with the exception of Gz) or Gq subfamilies of heterotrimeric G-proteins leaving Gz, G12 or G13 as the strongest candidates for Ge.