Document Detail


EP₃ receptors mediate PGE₂-induced hypothalamic paraventricular nucleus excitation and sympathetic activation.
MedLine Citation:
PMID:  21803943     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prostaglandin E(2) (PGE(2)), an important mediator of the inflammatory response, acts centrally to elicit sympathetic excitation. PGE(2) acts on at least four E-class prostanoid (EP) receptors known as EP(1), EP(2), EP(3), and EP(4). Since PGE(2) production within the brain is ubiquitous, the different functions of PGE(2) depend on the expression of these prostanoid receptors in specific brain areas. The type(s) and location(s) of the EP receptors that mediate sympathetic responses to central PGE(2) remain unknown. We examined this question using PGE(2), the relatively selective EP receptor agonists misoprostol and sulprostone, and the available selective antagonists for EP(1), EP(3), and EP(4). In urethane-anesthetized rats, intracerebroventricular (ICV) administration of PGE(2), sulprostone or misoprostol increased renal sympathetic nerve activity, blood pressure, and heart rate. These responses were significantly reduced by ICV pretreatment with the EP(3) receptor antagonist; the EP(1) and EP(4) receptor antagonists had little or no effect. ICV PGE(2) or misoprostol increased the discharge of neurons in the hypothalamic paraventricular nucleus (PVN). ICV misoprostol increased the c-Fos immunoreactivity of PVN neurons, an effect that was substantially reduced by the EP(3) receptor antagonist. Real-time PCR detected EP(3) receptor mRNA in PVN, and immunohistochemical studies revealed sparsely distributed EP(3) receptors localized in GABAergic terminals and on a few PVN neurons. Direct bilateral PVN microinjections of PGE(2) or sulprostone elicited sympathoexcitatory responses that were significantly reduced by the EP(3) receptor antagonist. These data suggest that EP(3) receptors mediate the central excitatory effects of PGE(2) on PVN neurons and sympathetic discharge.
Authors:
Zhi-Hua Zhang; Yang Yu; Shun-Guang Wei; Yoshiko Nakamura; Kazuhiro Nakamura; Robert B Felder
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-29
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  301     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-29     Completed Date:  2011-11-22     Revised Date:  2013-02-08    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1559-69     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Cerebrovascular Circulation / drug effects
Cyclooxygenase 2 / biosynthesis,  genetics
Dinoprostone / administration & dosage,  analogs & derivatives,  pharmacology*
Electrophysiological Phenomena
Fluorescent Antibody Technique
Heart Rate / drug effects
Hemodynamics / drug effects
Immunohistochemistry
Injections, Intraventricular
Kidney / drug effects,  innervation
Male
Microcirculation / physiology
Misoprostol / administration & dosage,  pharmacology
Paraventricular Hypothalamic Nucleus / blood supply,  drug effects*
Proto-Oncogene Proteins c-fos / biosynthesis
Rats
Rats, Sprague-Dawley
Receptors, Prostaglandin E, EP3 Subtype / physiology*
Reverse Transcriptase Polymerase Chain Reaction
Stimulation, Chemical
Sympathetic Nervous System / drug effects*
Grant Support
ID/Acronym/Agency:
R01 HL073986-05A2/HL/NHLBI NIH HHS; R01 HL073986-06/HL/NHLBI NIH HHS; R01 HL073986-07/HL/NHLBI NIH HHS; R01 HL073986-08/HL/NHLBI NIH HHS; R01-HL-073986/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-fos; 0/Receptors, Prostaglandin E, EP3 Subtype; 363-24-6/Dinoprostone; 59122-46-2/Misoprostol; 60325-46-4/sulprostone; EC 1.14.99.1/Cyclooxygenase 2
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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