title: Potential methodologic problems with in vivo immunoneutralization of pancreatic polypeptide.
abstract: Dogs with chronic pancreatic fistulae were given 0.5 ml of nonimmune rabbit serum or antibody S5, an antibody raised against the C-terminal pancreatic polypeptide (PP) hexapeptide. A 3-h infusion of secretin (125 ng/kg/h) and CCK8 (50 ng/kg/h) was started 30 min after injecting serum. Exogenous BPP (400 pmol/kg/h) was administered during the middle secretin/CCK hour. In a second protocol, 30 min after injecting nonimmune serum or PP-anti-serum, the animals were fed 15 g/kg cooked ground beef. Pretreatment with S5 enhanced secretin/CCK-induced bicarbonate outputs; protein outputs did not differ. Exogenous BPP inhibited pancreatic secretion, even in S5-treated animals. Meal-induced pancreatic secretion was not altered by S5 pretreatment. Significant increments in PP were measured by radioimmunoassay during administration of secretin/CCK and during BPP infusion. Anti-PP pretreatment abolished the former and significantly decreased, but did not abolish, the latter. The meal evoked significant postprandial increments in PP which were essentially abolished following S5 pretreatment. A physiological role for PP cannot be proved or refuted because antiserum pretreatment failed to block the effects of exogenous hormone. The latter must be established before excluding a peptide's physiological role based on negative in vivo immunoneutralization data.
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D004285:Dogs; D004435:Eating; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000037:antagonists & inhibitors* / Q000276:immunology; D011506:Proteins / Q000378:metabolism; D012633:Secretin / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001639:Bicarbonates; D011506:Proteins; D012633:Secretin; D010191:Pancreatic Polypeptide; D012844:Sincalide