Document Detail


Regulation of the cGMP-cPKG pathway and large-conductance Ca2+-activated K+ channels in uterine arteries during the ovine ovarian cycle.
MedLine Citation:
PMID:  19920217     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Liaqat H Khan; Charles R Rosenfeld; Xiao-Tie Liu; Ronald R Magness
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-11-17
Journal Detail:
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:
Created Date:  2010-08-17     Completed Date:  2010-09-01     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E222-8     Citation Subset:  IM    
Affiliation:
Division of Neonatal-Perinatal Medicine, University of Texas Southwestern Medical School, Dallas, Texas, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
HD-008783/HD/NICHD NIH HHS; HL-49210/HL/NHLBI NIH HHS; HL87144/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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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