INHIBITORY INTERACTIONS BETWEEN STIMULUS-SECRETION PATHWAYS IN THE EXOCRINE RAT PANCREAS

In many tissues the cellular responses mediated through different intr acellular messenger systems are mutually interactive. In the exocrine pancreas the secretagogues acting via adenosine cyclic monophosphate ( cAMP) and those acting via calcium-phosphoinositides can potentiate on e another. On the other hand, protein kinase C (PK-C) modulates recept or-induced responses in exocrine pancreatic cells and other cell types . Recording total protein output, monitored on-line at 280 nm, from su perfused rat pancreatic segments, we demonstrate that secretin (a cAMP -acting hormone) reduces the efficacy of the calcium-mediated secretag ogue cholecystokinin-octapeptide (CCK-8). Likewise, the PK-C activator 12,0, tetradecanoyl phorbol 13 acetate (TPA) reduces both the efficac y of secretin and the potency of cholecystokinin. Thus, the hypothesis of potentiation between different stimulus-secretion coupling mechani sms must be revised, and receptor-activated responses in the exocrine pancreas must be considered a complex model with multiple inhibitory a nd stimulatory interactions.