Pituitary adenylate cyclase-activating polypeptide in intrinsic and extrinsic nerves of the rat pancreas

Pituitary adenylate cyclase-activating polypeptide (PACAP) is the latest me mber of the vasoactive intestinal polypeptide (VIP) family of neuropeptides present in nerve fibres in many peripheral organs. Using double immunohist ochemistry, with VIP as a marker for intrinsic innervation and calcitonin-g ene related peptide (CGRP) as a marker for mainly extrinsic innervation, th e distribution and localization of PACAP were studied in the rat pancreas. PACAP was demonstrated in nerve fibres in all compartments of the pancreas and in a subpopulation of intrapancreatic VIP-containing ganglion cells. PA CAP and VIP were co-stored in intra- and interlobular nerve fibres innervat ing acini, blood vessels, and in nerve fibres within the islets of Langerha ns. No PACAP immunoreactivity was observed in the islet cells. Another popu lation of PACAP-immunoreactive nerve fibres co-localized with CGRP innervat ed ducts, blood vessels and acini. PACAP/CGRP-positive nerve fibres were al so demonstrated within the islets. Neonatal capsaicin reduced the PACAP-38 concentration by approximately 50%, and accordingly a marked reduction in P ACAP/CGRP-immunoreactive nerve fibres in the exocrine and endocrine pancrea s was observed. Bilateral subdiaphragmatic vagotomy caused a slight but sig nificant decrease in the PACAP-38 concentration compared with controls. In conclusion, PACAP-immunoreactive nerve fibres in the rat pancreas seem to h ave dual origin: extrinsic, most probably sensory fibres co-storing CGRP; a nd intrinsic, constituting a subpopulation of VIP-containing nerve cell bod ies and fibres innervating acinar cells and islet cells. Our data provide a morphological basis for the reported effects of PACAP in the pancreas and suggest that PACAP-containing nerves in the rat pancreas may have both effe rent and sensory functions.