Effects of P(1) and P2 Receptor Antagonists on Beta, Gamma-methyleneATP- and CGS21680-induced Cyclic AMP Formation in NG108-15 Cells

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2000 Feb 29

PMID 10694235

Citations 2

Authors

S Ohkubo

J Kimura

H Nakanishi

I Matsuoka

Affiliations

Soon will be listed here.

Abstract

1. We have previously shown that ATP increased cyclic AMP in NG108-15 cells, which was inhibited by P(1) receptor antagonist methylxanthines. In the present study, we examined the effects of P(1) and P2 receptor antagonists on cyclic AMP formation induced by beta,gamma-methyleneATP (beta,gamma-MeATP) and CGS21680, an A(2A) adenosine receptor agonist, in NG108-15 cells. 2. beta,gamma-MeATP and CGS21680 increased intracellular cyclic AMP with EC(50) values of 8. 0+/-0.98 microM (n=4) and 42+/-7.5 nM (n=4), respectively. 3. Several P(1) receptor antagonists inhibited both beta,gamma-MeATP- and CGS21680-induced cyclic AMP increase with a similar rank order of potency; ZM241385>CGS15943>XAC>DPCPX. However, the pK(i) values of these antagonists for beta,gamma-MeATP were larger than those for CGS21680. 4. Alloxazine, a P(1) receptor antagonist, and several P2 receptor antagonists (PPADS, iPPADS, reactive blue-2) inhibited beta, gamma-MeATP-induced response, while these antagonists little affected CGS21680-induced one. Suramin was effective only for beta, gamma-MeATP-induced response at 1 mM. 5. 2-chloroadenosine (2CADO) and 2-chloroATP (2ClATP) increased cyclic AMP with similar potencies. The effects of these agonists were both inhibited by ZM241385, but only 2ClATP-induced response was inhibited by PPADS. 6. ATP- and beta, gamma-MeATP-induced responses were little affected by alpha, beta-methyleneADP, a 5'-nucleotidase inhibitor. 7. These results clearly demonstrate that ATP-stimulated cyclic AMP formation can be distinguished from the A(2A) receptor agonist-induced one by using the several P(1) and P2 receptor antagonists.

Citing Articles

Inhibition of adenylyl cyclase by neuronal P2Y receptors.

Unterberger U, Moskvina E, Scholze T, Freissmuth M, Boehm S Br J Pharmacol. 2002; 135(3):673-84.

PMID: 11834615 PMC: 1573178. DOI: 10.1038/sj.bjp.0704514.

Ecto-alkaline phosphatase in NG108-15 cells : a key enzyme mediating P1 antagonist-sensitive ATP response.

Ohkubo S, Kimura J, Matsuoka I Br J Pharmacol. 2001; 131(8):1667-72.

PMID: 11139445 PMC: 1572508. DOI: 10.1038/sj.bjp.0703750.

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