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A2B adenosine receptor inhibition by the dihydropyridine calcium channel blocker nifedipine involves colonic fluid secretion.


ABSTRACT: The adenosine A2B receptor is a critical protein in intestinal water secretion. In the present study, we screened compound libraries to identify inhibitors of the A2B receptor and evaluated their effect on adenosine-induced intestinal fluid secretion. The screening identified the dihydropyridine calcium antagonists nifedipine and nisoldipine. Their respective affinities for the A2B receptor (Ki value) were 886 and 1,399?nM. Nifedipine and nisoldipine, but not amlodipine or nitrendipine, inhibited both calcium mobilization and adenosine-induced cAMP accumulation in cell lines. Moreover, adenosine injection into the lumen significantly increased fluid volume in the colonic loop of wild-type mice but not A2B receptor-deficient mice. PSB-1115, a selective A2B receptor antagonist, and nifedipine prevented elevated adenosine-stimulated fluid secretion in mice. Our results may provide useful insights into the structure-activity relationship of dihydropyridines for A2B receptor. As colonic fluid secretion by adenosine seems to rely predominantly on the A2B receptor, nifedipine could be a therapeutic candidate for diarrhoea-related diseases.

SUBMITTER: Asano T 

PROVIDER: S-EPMC7044278 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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A<sub>2B</sub> adenosine receptor inhibition by the dihydropyridine calcium channel blocker nifedipine involves colonic fluid secretion.

Asano Teita T   Noda Yuto Y   Tanaka Ken-Ichiro KI   Yamakawa Naoki N   Wada Mitsuhito M   Mashimo Tadaaki T   Fukunishi Yoshifumi Y   Mizushima Tohru T   Takenaga Mitsuko M  

Scientific reports 20200226 1


The adenosine A<sub>2B</sub> receptor is a critical protein in intestinal water secretion. In the present study, we screened compound libraries to identify inhibitors of the A<sub>2B</sub> receptor and evaluated their effect on adenosine-induced intestinal fluid secretion. The screening identified the dihydropyridine calcium antagonists nifedipine and nisoldipine. Their respective affinities for the A<sub>2B</sub> receptor (K<sub>i</sub> value) were 886 and 1,399 nM. Nifedipine and nisoldipine,  ...[more]

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