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Article
PGE2 action in human coronary artery smooth muscle: Role of potassium channels and signaling cross-talk
Journal of vascular research
  • Shu Zhu, Philadelphia College of Osteopathic Medicine
  • Guichun Han
  • Richard E. White
Document Type
Article
Publication Date
1-1-2002
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 μM PGE2 opens a high-conductance (∼200 pS), calcium-stimulated potassium (BKCa) 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 BKCa 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 BKCa 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. Copyright © 2002 S. Karger AG, Basel.
Comments

This article was published in Journal of vascular research, Volume 39, Issue 6, Pages 477-488.

The published version is available at http://dx.doi.org/10.1159/000067201.

Copyright © 2002 Karger.

Citation Information
Shu Zhu, Guichun Han and Richard E. White. "PGE2 action in human coronary artery smooth muscle: Role of potassium channels and signaling cross-talk" Journal of vascular research Vol. 39 Iss. 6 (2002) p. 477 - 488
Available at: http://works.bepress.com/shu_zhu/11/