| Regulation of the cGMP-cPKG pathway and large-conductance Ca2+-activated K+ channels in uterine arteries during the ovine ovarian cycle. | |
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MedLine Citation:
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PMID: 19920217 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The follicular phase of the ovine ovarian cycle demonstrates parallel increases in ovarian estrogens and uterine blood flow (UBF). Although estrogen and nitric oxide contribute to the rise in UBF, the signaling pathway remains unclear. We examined the relationship between the rise in UBF during the ovarian cycle of nonpregnant sheep and changes in the uterine vascular cGMP-dependent pathway and large-conductance Ca(2+)-activated K(+) channels (BK(Ca)). Nonpregnant ewes (n = 19) were synchronized to either follicular or luteal phase using a vaginal progesterone-releasing device (CIDR), followed by intramuscular PGF(2alpha), CIDR removal, and treatment with pregnant mare serum gonadotropin. UBF was measured with flow probes before tissue collection, and second-generation uterine artery segments were collected from nine follicular and seven luteal phase ewes. The pore-forming alpha- and regulatory beta-subunits that constitute the BK(Ca), soluble guanylyl cyclase (sGC), and cGMP-dependent protein kinase G (cPKG) isoforms (cPKG(1alpha) and cPKG(1beta)) were measured by Western analysis and cGMP levels by RIA. BK(Ca) subunits were localized by immunohistochemistry. UBF rose >3-fold (P < 0.04) in follicular phase ewes, paralleling a 2.3-fold rise in smooth muscle cGMP and 32% increase in cPKG(1alpha) (P < 0.05). sGC, cPKG(1beta), and the BK(Ca) alpha-subunit were unchanged. Notably, expression of beta(1)- and beta(2)-regulatory subunits rose 51 and 79% (P <or= 0.05), respectively. Increases in endogenous ovarian estrogens in follicular-phase ewes result in increases in UBF associated with upregulation of the cGMP- and cPKG-dependent pathway and increased vascular BK(Ca) beta/alpha-subunit stoichiometry, suggesting enhanced BK(Ca) activation contributes to the follicular phase rise in UBF. |
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Authors:
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Liaqat H Khan; Charles R Rosenfeld; Xiao-Tie Liu; Ronald R Magness |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-11-17 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 298 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-08-17 Completed Date: 2010-09-01 Revised Date: 2011-07-22 |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E222-8 Citation Subset: IM |
Affiliation:
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Division of Neonatal-Perinatal Medicine, University of Texas Southwestern Medical School, Dallas, Texas, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cyclic GMP / metabolism Cyclic GMP-Dependent Protein Kinases / metabolism Estrous Cycle / metabolism* Female Large-Conductance Calcium-Activated Potassium Channels / metabolism* Nitric Oxide / metabolism Ovarian Follicle / growth & development Ovulation / metabolism Second Messenger Systems / physiology Sheep Signal Transduction / physiology Statistics, Nonparametric Uterine Artery / metabolism* Uterus / blood supply* |
| Grant Support | |
ID/Acronym/Agency:
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HD-008783/HD/NICHD NIH HHS; HL-49210/HL/NHLBI NIH HHS; HL87144/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Large-Conductance Calcium-Activated Potassium Channels; 10102-43-9/Nitric Oxide; 7665-99-8/Cyclic GMP; EC 2.7.11.12/Cyclic GMP-Dependent Protein Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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