The messenger role of Ca+2, cyclic nucleotides and inositol triphosphates in the stimulation of pepsinogen and mucous secretion were studied using isolated pig [correction of nug] gastric chief cells and guinea pig mucous cells, resp. Pepsinogen secretion was stimulated by agents either working at the postreceptor adenylate cyclase (AC) level (db-cAMP, forskolin) or after 12-o-tetradecanoyl-phorbol-13-acetate (TPA) stimulation of protein kinase C (PK C). Similar secretory effects were observed with histamine (H), carbachol (C) and cholecystokinin (CCK). [Ca-2] in was elevated by C and by CCK, but not by H in both types of cells. Like TPA, both C and CCK, but not H, stimulated the Ca+2-sensitive particulate PK C. H increased the activity of cAMP-dependent PK A. PGE2, C and CCK were found to increase inositol-1,4,5-triphosphate content in mucous cells. The findings indicate that two pathways of the regulation of pepsinogen and mucous secretion (AC-cAMP-PK C and phosphoinositol breakdown cascade) can act synergistically.