Peripheral cholecystokinin(A) and cholecystokinin(B) receptors mediate stimulation of gastric pepsinogen and acid secretion following intracerebroventricular injection of cholecystokinin-8-sulphate

Background. Peptides of cholecystokinin family regulate various physiologic al actions by acting at level of central nervous system. Aims. To: 1) investigate possible influence of central cholecystokinin path ways on gastric pepsinogen and acid secretions; 2) characterize pharmacolog ical profile and location of cholecystokinin receptor subtypes involved in gastric effects of centrally applied cholecystokinin-8-sulphate (cholecysto kinin-8S). Methods. Urethane-anaesthetized rats were subjected to continuous perfusion of gastric lumen. Pepsin levels in perfusate were determined by enzymatic assay based on spectrophotometric measurement of products generated by pept ic digestion of bovine haemoglobin. Acidity was measured by automatic poten tiometric titration of hydrogen ions. Results. Following intracerebroventricular injection, cholecystokinin-8S in creased both pepsinogen and acid output. In addition, intravenous cholecyst okinin-8S stimulated peptic and acid secretions more promptly and at lower doses than after central injection. Stimulant effects of centrally applied cholecystokinin-8S were not affected by intracerebroventricular injection o f devazepide (cholecystokinin(A) receptor antagonist) or L-365,260 (cholecy stokinin(B) receptor antagonist) or by bilateral vagotomy. However intraven ous devazepide partly antagonized pepsigogue action of int cerebroventricul ar cholecystokinin-8S without affecting its acid hypersecretory effect, whe reas after intravenous injection of L-365,260 peptic hypersecretion evoked by intracerebroventricular cholecystokinin-8S was partially prevented and a cid response was completely blocked. Similar effects were exerted by intrav enous devazepide and L-365,260 against intravenous cholecystokinin-8S. A co mplete blockade of pepsigogue effects induced by intracerebroventricular or intravenous cholecystokinin-8S was obtained after combined intravenous tre atment with devazepide plus L-365,260. Gastric hypersecretory effects of in travenous cholecystokinin-8S were not modified by bilateral vagotomy. Conclusions. Increase in pepsinogen output evoked by centrally applied chol ecystokinin-8S does not depend on interaction with central nervous sites. F ollowing central or parenteral injection of cholecystokinin-8S, increase in peptic secretion would result from activation of both peripheral cholecyst okinin(A) and (B) receptors presumably located at the level of gastric muco sa.