To elucidate the regulatory mechanism of
acid secretion by
cholecystokinin (CCK) in vivo, we compared the effects of CCK and
gastrin on
acid secretion and
histidine decarboxylase (HDC) activity. We also examined the effects of
MK-329, a specific antagonist for pancreatic-type
CCK receptor, and L-365,260, a specific antagonist for
gastrin-type
CCK receptor, on the action of CCK. Graded doses of CCK or
gastrin were intravenously infused into conscious rats with
gastric fistula.
Gastrin-17 I infusion up to 10 nmol/kg/h resulted in dose-related increases in
acid secretion.
CCK-8 infusion also caused an increase in
acid secretion. However, it reached a peak with 0.3 nmol/kg/h
CCK-8 and attenuated with higher concentrations of
CCK-8. This attenuating effect of a higher dose of CCK was reversed by
MK-329, but not by L-365,260. Both CCK and
gastrin were potent in increasing fundic HDC activity, and the effect of CCK on HDC activity was significantly inhibited by L-365,260, but not by
MK-329. Taken together, the present study suggests that CCK and
gastrin stimulate
histamine formation via a
gastrin-type
CCK receptor, and the attenuating action of CCK with higher concentrations on
acid secretion in vivo is mediated by a pancreatic-type
CCK receptor.