title: Peripheral cholecystokinin A and cholecystokinin B receptors mediate stimulation of gastric pepsinogen and acid secretion following intracerebroventricular injection of cholecystokinin-8-sulphate.
abstract: BACKGROUND
  Peptides of cholecystokinin family regulate various physiological actions by acting at level of central nervous system.
  
  
  OBJECTIVE
  To: 1) investigate possible influence of central cholecystokinin pathways on gastric pepsinogen and acid secretions; 2) characterize pharmacological profile and location of cholecystokinin receptor subtypes involved in gastric effects of centrally applied cholecystokinin-8-sulphate (cholecystokinin-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 peptic digestion of bovine haemoglobin. Acidity was measured by automatic potentiometric titration of hydrogen ions.
  
  
  RESULTS
  Following intracerebroventricular injection, cholecystokinin-8S increased both pepsinogen and acid output. In addition, intravenous cholecystokinin-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 of devazepide (cholecystokinin A receptor antagonist) or L-365,260 (cholecystokinin B receptor antagonist) or by bilateral vagotomy. However, intravenous devazepide partly antagonized pepsigogue action of intracerebroventricular cholecystokinin-8S without affecting its acid hypersecretory effect, whereas after intravenous injection of L-365,260 peptic hypersecretion evoked by intracerebroventricular cholecystokinin-8S was partially prevented and acid response was completely blocked. Similar effects were exerted by intravenous devazepide and L-365,260 against intravenous cholecystokinin-8S. A complete blockade of pepsigogue effects induced by intracerebroventricular or intravenous cholecystokinin-8S was obtained after combined intravenous treatment with devazepide plus L-365,260. Gastric hypersecretory effects of intravenous cholecystokinin-8S were not modified by bilateral vagotomy.
  
  
  CONCLUSIONS
  Increase in pepsinogen output evoked by centrally applied cholecystokinin-8S does not depend on interaction with central nervous sites. Following central or parenteral injection of cholecystokinin-8S, increase in peptic secretion would result from activation of both peripheral cholecystokinin A and B receptors presumably located at the level of gastric mucosa.
authors.affiliation: Department of Oncology, University of Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Blandizzi
authors.forename: G
authors.initials: G
authors.lastname: Lazzeri
authors.forename: D
authors.initials: D
authors.lastname: Carignani
authors.forename: R
authors.initials: R
authors.lastname: Colucci
authors.forename: F
authors.initials: F
authors.lastname: Baschiera
authors.forename: M
authors.initials: M
authors.lastname: Tognetti
authors.forename: G
authors.initials: G
authors.lastname: Placanica
authors.forename: M
authors.initials: M
authors.lastname: Del Tacca
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology*; D020109:Devazepide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005744:Gastric Acid / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D020116:Pepsinogen A / Q000187:drug effects* / Q000378:metabolism; D010671:Phenylurea Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D013268:Stimulation, Chemical; D013997:Time Factors
chemical_list: D001570:Benzodiazepinones; D006727:Hormone Antagonists; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C058121:L 365260; D020116:Pepsinogen A; D002766:Cholecystokinin; D020109:Devazepide