| The presence and function of phosphodiesterase type 5 in the rat myometrium. | |
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MedLine Citation:
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PMID: 14749671 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Cyclic nucleotide phosphodiesterases (PDEs) are a diverse enzyme group with multiple regulatory properties and wide tissue distribution. Such activity includes cyclic adenosine (cAMP) and guanosine monophosphate (cGMP) breakdown. The type 5 isoform (PDE-5, cGMP specific) is the target of specific antagonists (ie, sildenafil, Viagra). We tested the hypothesis that PDE-5 is present in rat myometrium and modulates myometrial activity. STUDY DESIGN: Full-thickness uterine wall was collected from nonpregnant (n=3) and pregnant Sprague-Dawley rats on days 10 (n=4), 17 (n=6), 22 nonlabor (n=5), and 22 during term labor (TL, n=4). Preterm labor (PTL, n=3) was induced in some animals on day 16 with 15 mg/kg mifepristone (RU 486). Tissue samples were prepared for Western blotting using a monoclonal antibody against rodent PDE-5. In a second series, cumulative doses of sildenafil (0.005, 0.05, 0.5, 5 mg/kg, intraperitoneal) were administered and the effect on uterine contractility recorded in vivo during term (TL, n=7) and preterm labor (PTL, n=6). Saline solution-injected rats provided temporal control. Uterine contractility was estimated from intrauterine pressure (IP) measured electronically with a sensor tip pressure catheter. Heart rate was recorded simultaneously using electrodes attached to the chest and connected to the same data acquisition system. RESULTS: PDE-5 immunoreactivity was present in the nonpregnant rat uterus and at all gestational times studied, although the expression was unaffected by either pregnancy or the state of labor (preterm or term). A dominant antibody-specific band was identified at 86 kd in the uterine samples, contrasting with lung where the 100-kd PDE-5 isoform was most abundant. Two additional lower molecular weight (55 and 32 kd) bands were also identified as antibody specific. Despite the lack of change in PDE-5 during pregnancy, sildenafil reduced IP during TL and PTL beginning at 0.5 mg/kg. The highest dose of sildenafil reduced IP during both TL and PTL by 45% and 59% of baseline, respectively (two-way analysis of variance, P<.01). This effect was not accompanied by changes in heart rate. CONCLUSION: PDE-5 is constitutively present in the rat uterine wall. There was no observed change in the PDE-5 protein expression throughout pregnancy. In contrast to the lung, the uterus expresses an 80-kd PDE-5 isoform. Sildenafil in pharmacologic doses inhibits mechanical uterine activity and might be of benefit if selectively used for treatment of preterm labor. |
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Authors:
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Catalin S Buhimschi; Robert E Garfield; Carl P Weiner; Irina A Buhimschi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: American journal of obstetrics and gynecology Volume: 190 ISSN: 0002-9378 ISO Abbreviation: Am. J. Obstet. Gynecol. Publication Date: 2004 Jan |
Date Detail:
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Created Date: 2004-01-29 Completed Date: 2004-02-25 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370476 Medline TA: Am J Obstet Gynecol Country: United States |
Other Details:
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Languages: eng Pagination: 268-74 Citation Subset: AIM; IM |
Affiliation:
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Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University, New Haven, CT 06520, USA. catalin.buhimschi@yale.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3',5'-Cyclic-GMP Phosphodiesterases Animals Cyclic Nucleotide Phosphodiesterases, Type 5 Female Labor, Obstetric / metabolism* Myometrium / enzymology* Phosphodiesterase Inhibitors / pharmacology Phosphoric Diester Hydrolases / metabolism* Piperazines / pharmacology Pregnancy Pregnancy, Animal / metabolism* Purines Rats Rats, Sprague-Dawley Sulfones Uterine Contraction / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Phosphodiesterase Inhibitors; 0/Piperazines; 0/Purines; 0/Sulfones; 139755-83-2/sildenafil; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC 3.1.4.35/3',5'-Cyclic-GMP Phosphodiesterases; EC 3.1.4.35/Cyclic Nucleotide Phosphodiesterases, Type 5; EC 3.1.4.35/Pde5a protein, rat |
| Comments/Corrections | |
Comment In:
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Am J Obstet Gynecol. 2006 Jul;195(1):184-5
[PMID:
16813753
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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