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The possibility of an intrinsic renin-angiotensin system (RAS) in the pancreas has been raised by previous studies in which immunohistochemical examination showed the presence of angiotensin II and its receptor subtypes, type 1 (AT1) and type 2 (AT2). In the present study, gene expression of several key RAS components was investigated by reverse-transcription PCR. mRNA expression for angiotensinogen, renin and angiotensin II receptor subtypes, AT1a, AT1b and AT2 was shown. The presence of angiotensinogen protein, the mandatory component for an intrinsic RAS, was demonstrated by Western blotting and localized by immunohistochemistry to the epithelia and endothelia of pancreatic ducts and blood vessels respectively. Immunoblot analysis detected a predominant protein band of about 60 kDa in the pancreas. This was consistent with the predicted value for angiotensinogen as reported in other tissues. Together with previous findings, the present study shows that the rat pancreas expresses the major RAS component genes, notably angiotensinogen and renin, required for intracellular formation of angiotensin II. The data support the notion of an intrinsic RAS in the rat pancreas which may play a role in the regulation of pancreatic functions.
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The present study investigated the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of electrogenic anion secretion by the rat cauda epididymal epithelium. PACAP38, which has been shown to affect secretory function in various exocrine and endocrine tissues, gave rise to a concentration-dependent increase in the short-circuit current (Isc). The PACAP38 effect was restricted to the apical aspect of the epididymal cells. The Isc response to PACAP38 was abolished in Cl-(-)free solution and completely inhibited by the Cl- channel blocker, diphenylamine-dicarboxylic acid. The Isc response to PACAP38 was also suppressed by pretreatment of the cells with the adenylate cyclase inhibitor, MDL12330A. The localization of PACAP38 was further investigated using an immunohistochemical technique. PACAP38 immunoreactivity was observed in the cauda epididymal tubules as well as in the cultured epithelium, indicating its epithelial origin. The present results suggest that Cl- secretion in the epididymis may be regulated by PACAP38, which could be locally synthesized and released by the epithelial cells, in a paracrine or autocrine fashion.
