Development of secretory mechanisms in rat pancreas.

Mechanisms and development of secretory function were studied in rat pancreas in vitro. Amylase release from term fetal pancreas was refractory to stimulation by carbamylcholine chloride (carbachol) and cholecystokinin-octapeptide (CCK-OP), but was significantly augmented by calcium ionophore (A23187), DBcAMP, 8-Br-cGMP, and theophylline. The latter agent when combined with either cyclic nucleotide analogue further increased secretory responses. At 1 day and 8 days postnatally, responsiveness to carbachol and CCK-OP had been acquired because amylase secretion stimulated by these agents was brisk and at a level comparable to that found in mature tissue. Increasing extracellular calcium concentrations from 1.23 to 5.28 mM had no effect on basal amylase release in either the fetal or 8-day pancreas. No changes in intracellular cAMP concentrations were found at any age under experimental conditions used. Similarily, in fetal tissue, no changes in cGMP concentrations were found in response to carbachol or A23187. However, at 8 days of age, both agents produced two- to four-fold increases in tissue cGMP levels at 1, 2, and 5 min of incubation. These studies confirm that responsiveness to carbachol and CCK-OP is a maturational process in the pancreas that lags behind the development of intracellular processes involved in stimulus-secretion coupling.