1998
DOI: 10.1111/j.1472-8206.1998.tb00952.x
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YM022, a highly potent and selective CCKB antagonist inhibiting gastric acid secretion in the rat, the cat and isolated rabbit glands

Abstract: We investigated the effects of the novel CCKB/gastrin antagonist YM022 on gastric acid secretion in vivo and in vitro, compared to CI-988 and L365,260 as reference antagonists. In the anaesthetized rat, pentagastrin-induced stimulation of gastric acid secretion was dose-dependently and up to 100% inhibited by i.v. administration of YM022 with an ID50 of 0.009 +/- 0.0006 mumol/kg h in comparison to 0.6 +/- 0.03 and 3.40 +/- 0.05 mumol/kg h for CI-988 and L-365,260, respectively. In the gastric fistula cat, i.v.… Show more

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Cited by 7 publications
(5 citation statements)
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“…In the anaesthetized rat, L‐365 260 dose‐dependently inhibited pentagastrin‐induced stimulation of gastric acid secretion, with an ID 50 of 2.5 μmol kg −1 h −1 (Attoub et al 1998). Vagal nodose neuronal responses to CCK were monitored as previously described.…”
Section: Methodsmentioning
confidence: 99%
“…In the anaesthetized rat, L‐365 260 dose‐dependently inhibited pentagastrin‐induced stimulation of gastric acid secretion, with an ID 50 of 2.5 μmol kg −1 h −1 (Attoub et al 1998). Vagal nodose neuronal responses to CCK were monitored as previously described.…”
Section: Methodsmentioning
confidence: 99%
“…The structurally related benzodiazepines L‐365 260 and YM022 are selective antagonists for the human CCK‐B receptor subtype; L‐365 260 is a competitive antagonist, and YM022 behaves as an irreversible antagonist. YM022 has shown a higher potency than that of L‐365 260 in several animal bioassays (IC 50 0.0012 μmol L –1 and 2.8 μmol L –1 , respectively), 30 and a selectivity for CCK‐B/gastrin receptors 1000‐fold greater than for the CCK‐A receptor, 31 , 32 whereas the selectivity of L‐365 260 for the CCK‐B receptor was two orders of magnitude higher than for the CCK‐A receptor 29 . YM022 has shown a IC 50 of 7.4 nmol L –1 on a bioassay using the human CCK‐B receptor expressed in CHO cells, 33 and showed a selectivity for the human CCK‐B receptor 6000‐fold greater than the A type 34 .…”
Section: Discussionmentioning
confidence: 96%
“…However, sulfated CCK octapeptide has a much greater affinity to CCK A R than CCK B R while gastrin has a much greater affinity to CCK B R than CCK A R 20 . Indeed, the natriuretic and diuretic effects of gastrin were blocked by the selective CCK B R antagonist, CI-988 26,37 . While CCK B R is expressed in the renal proximal tubule 24,25 , CCK A R is not 38 .…”
Section: Discussionmentioning
confidence: 99%
“…We hypothesized, further, that this interaction is impaired in hypertension. To test these hypotheses, we studied the natriuretic effect of intrarenal arterial infusion of gastrin with or without co-infusion of a D 1 -like receptor agonist, fenoldopam, in the presence or absence of their respective antagonists, CI-988 (CCK B R antagonist) 26 and SCH23390 27,28 , D 1 -like receptor antagonist, in the normotensive Wistar-Kyoto (WKY) rat and the spontaneously hypertensive rat (SHR). We also studied the colocalization and physical and functional interactions between CCK B R and D 1 R in rat RPT cells.…”
Section: Introductionmentioning
confidence: 99%