Structure-function analyses of eicosanoid receptors. Physiologic and therapeutic implications.
Prostaglandins (PGs) are ubiquitous lipid mediators derived from cyclooxygenase (COX) metabolism of arachidonic acid that exert a broad range of physiologic activities including modulation of inflammation, ovulation, and arterial blood pressure. The physiologic actions of PGs are mediated in part by their interaction with specific G-protein-coupled PG receptors. Eight PG receptors have been cloned, including four for the major COX metabolite, PGE2. The physiologic roles of the PGE2 receptors have been investigated utilizing subtype-selective agonists, localization of receptor mRNA expression, and creation of mice with targeted disruption of PG receptor genes. These analyses have delineated discrete roles for the various PG receptor subtypes. Recent studies on mice lacking the PGE2 EP2 receptor have implicated the PGE2 EP2 receptor subtype in arterial dilatation and salt-sensitive hypertension, and also indicate that this receptor plays a key role in female fertility. The EP2 receptor may thus prove to be a productive target for pharmacological intervention in the treatment of hypertension and infertility.
Breyer
R M
RM
Department of Medicine (Division of Nephrology), Vanderbilt University School of Medicine, Nashville, Tennessee, USA. rich.breyer@mcmail.vanderbilt.edu
Kennedy
C R
CR
Zhang
Y
Y
Breyer
M D
MD
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators; D051379:Mice; D018345:Mice, Knockout; D010060:Ovulation / Q000502:physiology; D011247:Pregnancy; D018055:Receptors, Eicosanoid / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship
D018836:Inflammation Mediators; D018055:Receptors, Eicosanoid