title: Neuromodulation of guinea pig intestinal electrolyte transport by cholecystokinin octapeptide.
abstract: We examined the effect of cholecystokinin octapeptide on electrolyte transport across isolated guinea pig mucosa. Segments of distal ileum stripped of longitudinal muscle and bathed on both sides with a Krebs'-bicarbonate buffer responded to cholecystokinin octapeptide when studied under short-circuited conditions. Cholecystokinin octapeptide (0.5-50 nmol/L) evoked a transient (4-10-minute) increase in transepithelial potential difference and short-circuit current upon application to the serosal side. Maximal increases in short-circuit current, achieved at 50-500 nmol/L, were 67 +/- 11 microA/cm2, whereas half-maximal effects occurred at a concentration of 0.7 +/- 0.2 nmol/L. Pretreatment of the tissues with 0.5 mumol/L atropine reduced the maximal short-circuit response to cholecystokinin octapeptide by 53%. The change in short-circuit current due to cholecystokinin octapeptide was nearly abolished by pretreatment with 0.5 mumol/L tetrodotoxin, suggesting neuronal involvement. Cholecystokinin octapeptide-induced increases in short-circuit current were halved by removal of serosal buffer Ca2+ and were abolished in Cl(-)- and HCO3(-)-free buffer. The cholecystokin-receptor antagonists proglumide and lorglumide shifted the concentration-response curve for cholecystokinin octapeptide competitively to the right, having antagonists potencies of 130 and 0.03 mumol/L, respectively. Cerulein (0.1-500 nmol/L) also increased short-circuit current, whereas nonsulfated cholecystokinin octapeptide was ineffective. In conclusion, cholecystokinin octapeptide seems to act at neuronal cholecystokinin receptors to stimulate mucosal anion secretion, in part, by releasing acetylcholine.
authors.affiliation: NOVA Pharmaceutical Corporation, Baltimore, Maryland.
authors.forename: J F
authors.initials: JF
authors.lastname: Kachur
authors.forename: G S
authors.initials: GS
authors.lastname: Phillips
authors.forename: T S
authors.initials: TS
authors.lastname: Gaginella
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000378:metabolism*; D004594:Electrophysiology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000294:innervation; D008297:Male; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D003470:Culture Media; D004573:Electrolytes; D011949:Receptors, Cholecystokinin; D002034:Bumetanide; D013779:Tetrodotoxin; D001285:Atropine; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide; D002118:Calcium