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  • Title: Neuromodulation of guinea pig intestinal electrolyte transport by cholecystokinin octapeptide.
    Author: Kachur JF, Phillips GS, Gaginella TS.
    Journal: Gastroenterology; 1991 Feb; 100(2):344-9. PubMed ID: 1985032.
    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.
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