Action of pituitary adenylate cyclase-activating polypeptide on ion transport in guinea pig distal colon.

The aim of the present study was to investigate the action of pituitary adenylate cyclase-activating polypeptide (PACAP) on ion transport in the guinea pig distal colon. Submucosal/mucosal segments from distal colon were mounted in Ussing flux chambers, and increases in short-circuit current (Isc) were used as an index of secretion. Serosal addition of PACAP-38 and PACAP-27 produced concentration-dependent (10(-10)-10(-6) M) increases in Isc. Furosemide and chloride-free solutions significantly reduced the PACAP-evoked responses. Tetrodotoxin (TTX) completely blocked PACAP-evoked responses. Atropine significantly reduced the PACAP-evoked responses but did not abolish the responses. The results suggest that PACAP evokes chloride secretion through cholinergic and noncholinergic neural mechanism. Vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine amide, and helodermin evoked Isc in a concentration-dependent manner. Atropine reduced but did not abolish the VIP- and related peptides-evoked responses. TTX also significantly decreased the responses to higher concentrations of VIP and related peptides but did not abolish the responses. The results suggest that VIP and related peptides act on both submucosal neurons and the epithelial cell itself. VIP tachyphylaxis significantly decreased PACAP-38- and PACAP-27-evoked responses. These results provide evidence that PACAP recognizes, in some part, VIP receptors in the submucosal neurons to evoke chloride secretion.