SECRETION OF PANCREASTATINS FROM ISOLATED, PERFUSED, PORCINE ADRENAL-GLANDS

Pancreastatin is a 49 amino acid peptide with a C-terminal glycine ami de originally isolated from porcine pancreas. There are strong indicat ions that pancreastatin is derived from chromogranin A, since the amin o acid sequence 240-288 in porcine chromogranin A contains pancreastat in flanked by typical signals for proteolytic processing. Several mole cular forms of immunoreactive pancreastatin have been reported to be p resent in porcine adrenal medulla, but no information on the secretion of the peptides is available. We studied stimuli for the release of i mmunoreactive pancreastatin from adrenal glands as well as the molecul ar nature of the released immunoreactivity using isolated, perfused, p orcine adrenal glands with intact splanchnic nerve supply and a radioi mmunoassay specific for the C-terminal glycine amide of porcine pancre astatin in combination with chromatography. Stimulation of the splanch nic nerves greatly enhanced the release of immunoreactive pancreastati n by a mechanism that seems to involve cholinergic nicotinic transmiss ion. The pancreastatin immunoreactivity was due to large amounts of a N-terminally extended pancreastatin form, possibly corresponding to th e chromogranin A(1-288) fragment and small amounts of pancreastatin an d a C-terminal pancreastatin fragment. Adrenal extracts also contained unprocessed chromogranin A. We conclude that in the porcine adrenals at least 25% of chromogranin A is processed to smaller molecular forms with the pancreastatin sequence forming their C-terminus. These forms appear to be released in parallel with the catecholamines.