SPECIFIC MONOCLONAL-ANTIBODIES NEUTRALIZE THE ACTION OF PACAP-1-27 ORPACAP-1-38 ON INTESTINAL MUSCLE STRIPS IN-VITRO

The gut-brain neuropeptide pituitary adenylate cyclase activating poly peptide (PACAP) is a novel highly conserved member of the secretin-glu cagon-VIP peptide family comprising 38 or 27 amino acid residues. In t his study, we investigate the actions of PACAP 1-27 or PACAP 1-38 on j ejunal and caecal muscle strips from pig or guinea pig and demonstrate the neutralizing effect of two PACAP-specific monoclonal antibodies o f the IgG, subtype, RSP27II and RSP38. These antibodies were used to s et up assay systems specific for PACAP 1-27 or PACAP 1-38. Monoclonal antibody RSP27II recognizes exclusively PACAP 1-27, whereas RSP38 bind s only PACAP 1-38. PACAP 1-27 and PACAP 1-38 relax taenia caeci dose-d ependently in the presence of guanethidine and scopolamine. Both pepti des inhibit the spontaneous contractions of porcine jejunal muscle str ips equipotently. Monoclonal antibodies RSP27II and RSP38 specifically neutralize the actions of either exogenously applied or endogenously released PACAP. Thus, they represent processing-specific tools to exam ine the physiological role of both molecular forms of PACAP in the gas trointestinal tract.