PMID: 9160876Apr 1, 1997Paper

Isoform-specific regulation of adenylyl cyclase by oxidized catecholamines

Journal of Molecular and Cellular Cardiology
T EbinaY Ishikawa

Abstract

Both epinephrine and manganese are known to stimulate cAMP production in cardiac homogenates. When added together, however, they inhibited adenylyl cyclase catalytic activity. Type V adenylyl cyclase, the major isoform in the heart, was also inhibited when an increasing concentration of epinephrine was added in the presence of manganese. Inhibition was not dependent on the condition of stimulation or preparation of the enzyme. However, this inhibition was abolished in the presence of anti-oxidant. Other catecholamines, including dopamine and isoproterenol, as well as adrenochrome, an oxidized product of epinephrine, similarly inhibited the activity of this enzyme. Kinetic analyses revealed that the K(m) for the substrate ATP was unchanged, but the V(max) was significantly decreased. In contrast, type II adenylyl cyclase, a non-cardiac isoform, was resistant to such inhibition by adrenochrome and was somewhat stimulated by it. Thus, catecholamines, when oxidized, directly interacted with adenylyl cyclase in an isoform-specific manner in the absence of G proteins. Our findings suggest that adenylyl cyclase isoforms have different sensitivity to various stresses, including oxidative stress.

Citations

Nov 24, 2001·Brain Research. Developmental Brain Research·T A SlotkinF J Seidler
Jul 18, 2008·Journal of Medicinal Chemistry·Christine SchlickerClemens Steegborn
Oct 27, 2004·Circulation Journal : Official Journal of the Japanese Circulation Society·Takao NishizawaMitsuhiro Yokota
Nov 28, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Yosuke KatoMitsuhiro Yokota
Feb 13, 2003·Biomedical Chromatography : BMC·Fernando RemiãoA Ferrer-Correia
Jun 5, 2003·Expert Opinion on Therapeutic Targets·Kousaku IwatsuboYoshihiro Ishikawa
Jul 16, 1999·Molecular Endocrinology·C SchwenckeY Ishikawa
Jul 7, 2007·Physiological Reviews·Debbie Willoughby, Dermot M F Cooper
Apr 7, 1998·Endocrinology·Y ToyaY Ishikawa
Jun 18, 2002·Chemical Research in Toxicology·Fernando RemiãoMaria L Bastos

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