Inhibitory effect of CR-1409, a competitive inhibitor of cholecystokinin, on pancreatic exocrine secretion in the conscious rat.

Miyasaka, Kyoko; Nakamura, Rieko; Funakoshi, Akihiro; Kitani, Kenichi

doi:10.1620/tjem.155.165

Cited by 9 publications

(5 citation statements)

References 11 publications

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“…Previous experiments have shown that CR-1409 acts as a competitive inhibitor of CCK in vivo (MIYASAKA et al, 1988). Thus, we conclude that CR-1409 is a specific inhibitor of the CCK receptor of the pancreas, and is useful in studies on the physiological action of CCK.…”

Section: Discussionsupporting

confidence: 55%

“…One of these derivatives, CR-1409 (3, 4-dichloro-benzamido-N, N-dipentylglutaramic acid) was found to have 5,000-7,000 times the CCK-antagonistic effect of proglumide as determined by its effect on amylase release and gallbladder contraction (MAKOVEC et al, 1985;IWAMOTO et al, 1987;LoulE et al, 1988;NIEDERAU et a!.,1989). Previously, we reported that CR-1409 inhibits CCK-8 stimulated pancreatic secretion in vivo (MIYASAKA et al, 1988). In this work, for further study of the effect of CR-1409 on pancreatic exocrine secretion, we examined its effect on both dynamic amylase secretion using a perifusion apparatus and intracellular [Ca2 +]; mobilization stimulated by carbamyicholine (Cch), gastrinreleasing peptide (GRP), and caerulein, a CCK analogue in vitro.…”

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confidence: 99%

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The inhibitory effect of CR-1409 on amylase secretion and intracellular Ca2+ mobilization in rat pancreatic acini in vitro.

et al. 1989

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The inhibitory effects of CR-1409, a new glutaramic acid derivative developed as a cholecystokinin (CCK) receptor antagonist, on caerulein-stimulated amylase secretion and on intracellular Cat + ([Ca2 +];) mobilization were studied in isolated rat pancreatic acini. Pancreatic acini were prepared by collagenase digestion method and loaded with 1,uM fura-2/AM for measurement of the intracellular free Cat + concentration. Amylase release was examined by a perifusion method. Stimulation with 10 1 ° M caerulein, 10 -5 M carbachol, or 10 -8 M gastrin-releasing peptide (GRP) led to biphasic amylase release and increase in [Ca2+];. CR-1409 at 1 and 5 ,uM inhibited, by 50 and 84%, respectively, the amylase secretion and increase in [Ca2 +]; induced by 10 -10M caerulein, and 25µM CR-1409 completely inhibited both amylase secretion and increase in [Ca2+]i induced by caerulein. However, 25,uM CR-1409 did not inhibit unstimulated secretion of amylase or the secretions induced by carbachol and GRP, which are also mediated by changes in intracellular Ca2 + . We conclude that CR-1409 acts as a specific inhibitor of the CCK receptor in the pancreas, and is useful in studies on the involvement of the release and action of CCK in vitro.

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Section: Discussionsupporting

confidence: 55%

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confidence: 99%

The inhibitory effect of CR-1409 on amylase secretion and intracellular Ca2+ mobilization in rat pancreatic acini in vitro.

et al. 1989

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“…Therefore, we conclude that CCK contributes in part to pancreatic hypersecretion induced by neuromedin C in rats. However, CR-1409 did not abolish the stimulatory effect of neuromedin C. The dose of CR-1409 used was sufficient to inhibit the action of endogenously released CCK, but did not affect basal pancreatic secretion (16). Moreover, the increase in plasma CCK was transient.…”

Section: Discussionmentioning

confidence: 88%

“…Administration of CR-1409 at 0.3 mg/kg/h, which has been reported to be sufficient to inhibit endogenously released CCK (16), was started 30 min before neuromedin C infusion. Omeprazole (5 pmol/kg) (13,17) was given intraduodenally to reduce acid secretion 30 min before neuromedin C infusion.…”

Section: Experimental Designmentioning

confidence: 99%

Mechanisms of Stimulatory Effect of Neuromedin C on Pancreatic Exocrine Secretion in Conscious Rats

Okubo

Miyasaka

Matsumoto³

et al. 1994

Pancreas

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The mechanisms of the stimulatory effect of the bombesin-like peptide neuromedin C on pancreatic exocrine secretion were examined in conscious rats. Rats were prepared with cannulae draining bile and pancreatic juice separately. Intravenous infusion of 0.35 nmoykg/h of neuromedin C significantly increased the secretions of pancreatic bicarbonate and protein, and transiently increased the plasma cholecystokinin (CCK) concentration. The increase in pancreatic secretion persisted for 90 min, whereas the increase in plasma CCK was observed only after 15 and 30 min from the beginning of neuromedin C infusion. Intravenous infusion of CR-1409, a specific CCK-receptor antagonist, inhibited, but did not abolish, the protein secretion stimulated by neuromedin C. Intraduodenal infusion of a potent proton pump inhibitor, omeprazole, suppressed, but did not abolish, protein secretion induced by neuromedin C. Omeprazole abolished the increase in bicarbonate secretion produced by neuromedin C. These results indicate that neuromedin C induces release of CCK and that its induction of pancreatic hypersecretion is due to both its direct effect and CCK. The results also suggest that gastric hypersecretion may have a role in the bicarbonate hypersecretion induced by neuromedin C.

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“…There is no significant difference between control and atro pine-treated rat groups. lated pancreatic responses to BPJ diversion, elevating plasma CCK concentration mea sured by a bioassay to about 20.0 pM on average (n = 5) [27], Therefore, the contin uous infusion of this dose of cerulein was considered to produce a similar concentra tion of the plasma CCK level as produced by BPJ diversion [17], We had anticipated that the inhibition of endogenous PP release might result in an increase in pancreatic secretion in response to the stimulation, be cause PP has been considered to be an inhib itory hormone of pancreatic secretion [4][5][6][7][8][9][10][11][12], However, since this was not the case, the role of endogenous PP released by BPJ di version thus still remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Release of Pancreatic Polypeptide and Its Mechanism in Luminal Feedback Regulation in the Conscious Rat

Miyasaka

Funakoshi²,

Miyazaki³

et al. 1989

Digestion

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Exclusion of bile and pancreatic juice (BPJ) from the proximal intestine increases the release of pancreatic polypeptide (PP) from 4.4 to 14.3 pM and its increase was diminished by the intravenous infusion of atropine (100 μg/kg/h) in conscious rats. Neither intravenous bolus injection nor continuous infusion of cerulein did increase plasma PP concentration. It is suggested that the increase in plasma PP concentration produced by BPJ diversion is regulated by cholinergic mechanism, but not by cholecystokinin (CCK) released despite the known fact that BPJ diversion increases plasma CCK concentration.

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Inhibitory effect of CR-1409, a competitive inhibitor of cholecystokinin, on pancreatic exocrine secretion in the conscious rat.

Cited by 9 publications

References 11 publications

The inhibitory effect of CR-1409 on amylase secretion and intracellular Ca2+ mobilization in rat pancreatic acini in vitro.

The inhibitory effect of CR-1409 on amylase secretion and intracellular Ca2+ mobilization in rat pancreatic acini in vitro.

Mechanisms of Stimulatory Effect of Neuromedin C on Pancreatic Exocrine Secretion in Conscious Rats

Release of Pancreatic Polypeptide and Its Mechanism in Luminal Feedback Regulation in the Conscious Rat

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