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A direct link between LY83583, a selective repressor of cyclic GMP formation, and glutathione metabolism.

Abstract：

:LY83583 (6-anilino-5,8-quinolinedione), considered to be a relatively specific repressor of cyclic GMP formation, is shown in the present study to inhibit (K(i) = 3 microM) glutathione reductase from bovine intestinal mucosa. As glutathione disulphide has been reported to inhibit guanylate cyclase irreversibly [Braughler, Biochem Pharmacol 32: 811-818, 1983], the inhibition of glutathione reductase should affect the activity of guanylate cyclase and may thus have physiological implications in the action of endothelium-derived relaxation factor and the design of muscle relaxants. LY83583 is reduced by NADPH and glutathione reductase in aerobic media and this may offer a route to the metabolic activation of LY83583. These results may have significant implications for the design of heart-regulating drugs (e.g. those used in angina), such as glyceryl trinitrate, which act via guanylate cyclase.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Lüönd RM,McKie JH,Douglas KT

doi

10.1016/0006-2952(93)90236-p

subject

Has Abstract

pub_date

1993-06-22 00:00:00

pages

2547-9

issue

12

eissn

0006-2952

issn

1873-2968

pii

0006-2952(93)90236-P

journal_volume

45

pub_type

杂志文章

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