Negative feedback in NO/cGMP signalling.

Abstract:

:Most of the effects of the signalling molecule nitric oxide (NO) are mediated by the stimulation of the NO-sensitive GC (guanylate cyclase) and the subsequent increase in cGMP formation. The enzyme contains a prosthetic haem group, which mediates NO stimulation. In addition to the physiological activator NO, NO-sensitizers like the substance YC-1 sensitize the enzyme towards NO and may therefore have important pharmacological implications. Two isoforms of NO-sensitive GC have been identified to date that share regulatory properties, but differ in the subcellular localization. The more ubiquitously expressed alpha1beta1 heterodimer and the alpha2beta1 isoform are mainly expressed in brain. In intact cells, NO-induced cGMP signalling not only depends on cGMP formation, but is also critically determined by the activity of the enzymes responsible for cGMP degradation, e.g. PDE5 (phosphodiesterase 5). Recently, direct activation of PDE5 by cGMP was demonstrated, limiting the cGMP increase and thus functioning as a negative feedback. As the cGMP-induced PDE5 activation turned out to be sustained, in the range of hours, it is probably responsible for the NO-induced desensitization observed within NO/cGMP signalling.

journal_name

Biochem Soc Trans

authors

Koesling D,Mullershausen F,Lange A,Friebe A,Mergia E,Wagner C,Russwurm M

doi

10.1042/BST20051119

keywords:

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

1119-22

issue

Pt 5

eissn

0300-5127

issn

1470-8752

pii

BST20051119

journal_volume

33

pub_type

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