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EP₃ receptors mediate PGE₂-induced hypothalamic paraventricular nucleus excitation and sympathetic activation
Journal article   Open access   Peer reviewed

EP₃ receptors mediate PGE₂-induced hypothalamic paraventricular nucleus excitation and sympathetic activation

Zhi-Hua Zhang, Yang Yu, Shun-Guang Wei, Yoshiko Nakamura, Kazuhiro Nakamura and Robert B Felder
American journal of physiology. Heart and circulatory physiology, Vol.301(4), pp.H1559-1569
10/2011
DOI: 10.1152/ajpheart.00262.2011
PMCID: PMC3197370
PMID: 21803943
url
https://doi.org/10.1152/ajpheart.00262.2011View
Published (Version of record) Open Access

Abstract

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.
 Immunohistochemistry Sympathetic Nervous System - drug effects Misoprostol - administration & dosage Injections, Intraventricular Proto-Oncogene Proteins c-fos - biosynthesis Misoprostol - pharmacology Male Dinoprostone - administration & dosage Cyclooxygenase 2 - biosynthesis Microcirculation - physiology Heart Rate - drug effects Cyclooxygenase 2 - genetics Blood Pressure - drug effects Dinoprostone - pharmacology Kidney - drug effects Cerebrovascular Circulation - drug effects Rats Paraventricular Hypothalamic Nucleus - blood supply Reverse Transcriptase Polymerase Chain Reaction Rats, Sprague-Dawley Stimulation, Chemical Receptors, Prostaglandin E, EP3 Subtype - physiology Paraventricular Hypothalamic Nucleus - drug effects Animals Fluorescent Antibody Technique Dinoprostone - analogs & derivatives Kidney - innervation Hemodynamics - drug effects Electrophysiological Phenomena

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