Modulation of cyclic AMP accumulation in GH3 cells by a phorbol ester and thyroliberin

4 beta phorbol-12, 13-dibutyrate (PDBu) stimulated cyclic AMP accumulation in GH3 pituitary tumour cells in the presence of isobutylmethylxanthine. This effect persisted after preincubation of cells with cholera or pertussis toxins. In contrast, vasoactive intestinal polypeptide (VIP)-stimulated cyclic AMP accumulation was inhibited by PDBu in a dose dependent fashion (IC50 = 5.1 nM). Thyroliberin (TRH) had a similar, but non-additive, stimulatory effect on cyclic AMP accumulation with PDBu, however it did not inhibit VIP stimulation. These results suggest that TRH may stimulate cyclic AMP accumulation through protein kinase C and that stimulation of adenylate cyclase by PDBu and TRH may occur distal to the guanine nucleotide binding regulatory proteins, Ns and Ni.