PACAP EVOKES CHLORIDE SECRETION IN GUINEA-PIG DISTAL COLON

Pituitary adenylate cyclase activating polypeptide (PACAP) is a newly discovered neuropeptide distributed in the enteric nervous system of the gut. The effects of PACAP on ion transport in the guinea-pig distal colon were examined in muscle-stripped sheets of submucosa-mucosa set up in Ussing flux chambers. Serosal addition of PACAP27 or PACAP38 evoked a concentration-dependent increase in short-circuit current. In order to determine the ionic basis for the increase in short-circuit current induced by PACAP, furosemide and chloride-free solutions were used. The PACAP-evoked responses were reduced in chloride-free solution or after addition of furosemide. The results suggest that PACAP-evoked an increase in short-circuit current is mainly due to chloride secretion in guinea-pig distal colon. Muscarinic receptor blocker, atropine (10(-5) M) significantly reduced the PACAP-evoked responses but not abolished. Neural blockade, tetrodotoxin (1-2 x 10(-7) M) completely abolished the PACAP-evoked responses. These results suggest that PACAP evokes chloride secretion by activating cholinergic and noncholinergic neurons in the enteric nervous system. Since structure of PACAP is quite similar to that of VIP, effect of VIP on baseline short-circuit current was examined. VIP evoked an increase in short-circuit current similar to those of PACAP. The response was greatly reduced by atropine. However, VIP still evoked response even in the presence of tetrodotoxin. The results suggest that VIP-evoked an increase in short-circuit current acts both on enteric neurons and on eithelial cell itself. These results suggest that the mode of action of PACAP differs from that of VIP. Thus, the present results provide strong evidence for the involvement of PACAP in regulation of chloride secretion in the guinea-pig distal colon.