Atrial natriuretic factor and exocrine pancreas: effects on the secretory process

Immunoreactive atrial natriuretic factor (ANF) has recently been identified in pancreatic acinar cells. The current study therefore, was, designed to ascertain whether the atrial peptide exercises any biological effects on the exocrine pancreas. When isolated rat pancreatic acinar cells were incubated with rat ANF (8-33), a concentration-dependent increase in cGMP synthesis was observed (EC50 about 5 X 10(-9) M) with the peak response occurring within 2.5 min of exposure of the cells to the peptide. ANF did not affect basal or secretagogue (carbachol +/- DbcAMP, CCK-OP, or forskolin)-induced amylase secretion from acinar cells, nor did it affect [3H]thymidine incorporation into DNA or [3H]leucine incorporation into trichloroacetic acid-precipitable protein. ANF was also infused intravenously (0.01-0.25 micrograms/min) in rabbits with cannulated pancreatic ducts, and the peptide stimulated a dose-dependent secretion of cGMP into pancreatic juice. ANF, by itself, did not affect protein or fluid secretion from rabbit pancreas; when co-infused with secretin (0.1 CU/min), which is not an acinar cell secretagogue in rabbits, ANF increased fluid secretion in one of three animals tested. The data suggest that acinar cells possess functional ANF receptors, whose activation results in both synthesis and secretion of cGMP. Intra-acinar cell cGMP is not involved in the enzyme secretory process. Secreted nucleotide is not co-released with digestive hydrolases, and does not, by itself, appear to have an intraluminal effect on fluid secretion. The mechanism by which acinar cells secrete cGMP into pancreatic juice as well as the biological significance of intracellular (acinar), and extracellular (intraluminal) cGMP remain to be elucidated.