PGE ₂ Action in Human Coronary Artery Smooth Muscle: Role of Potassium Channels and Signaling Cross-Talk

Abstract

Cyclic AMP-stimulating agents are powerful vasodilators, but our knowledge of the signal transduction mechanisms of these agents, particularly in human arteries, is limited. We now report direct molecular effects of prostaglandin E₂ (PGE₂) on cultured human coronary artery smooth muscle cells (HCASMC). Patch-clamp studies revealed that 10 µ M PGE₂ opens a high-conductance (∼200 pS), calcium-stimulated potassium (BK_Ca) channel in intact HCASMC. In contrast, PGE₂ had no direct effect on channels in cell-free patches, indicating involvement of a soluble second messenger. Enzyme immunoassay demonstrated that PGE₂ enhances production of cAMP in HCASMC, but does not increase [cGMP]. Furthermore, forskolin, CPT-cAMP, or CPT-cGMP mimicked the stimulatory effect of PGE₂ on BK_Ca channel activity. Interestingly, the response to PGE₂ was unaffected by inhibiting the cAMP-dependent protein kinase, but was antagonized by inhibitors of the cGMP-dependent protein kinase (PKG). Furthermore, cAMP-stimulated PKG activity mimicked the effect of PGE₂. These studies suggest a novel PGE₂ action in human arteries: opening of BK_Ca channels via cAMP cross-activation of PKG in HCASMC. It is proposed that this signaling mechanism may mediate the vasodilatory response to cAMP-dependent agents in the human coronary and other vascular beds.

Journal

Journal ID (publisher-id): JVR

Journal ID (nlm-ta): J Vasc Res

Journal ID (doi): 10.1159/issn.1018-1172

Title: Journal of Vascular Research

Publisher: S. Karger AG

ISSN (Print): 1018-1172

ISSN (Electronic): 1423-0135

Publication date Subscription-year: 2002

Publication date (Print): December 2002

Publication date (Electronic): 17 January 2003

Volume: 39

Issue: 6

Pages: 477-488

Affiliations

^aDepartment of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Ga., USA, and ^bDepartment of Physiology, Dalian Medical University, Dalian, People’s Republic of China

Article

Publisher ID: 67201 Other ID: J Vasc Res 2002;39:477–488

DOI: 10.1159/000067201

PubMed ID: 12566973

Copyright statement: © 2002 S. Karger AG, Basel

License:

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Page count

Figures: 10, References: 30, Pages: 12

Product

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Categories

Subject: Research Paper