Bimodal regulation of adenylate cyclase by prostaglandin E2 receptors in porcine ciliary epithelium.
Prostaglandin E2 (PGE2) binding revealed that porcine ciliary epithelial membranes possess two subclasses of binding sites or receptors. Ciliary nonpigmented epithelial (NPE) membranes have two binding sites (Kd,1 = 35 x 10(-9) M, Bmax,1 = 485 x 10(-12) mol/mg protein; Kd,2 = 0.723 x 10(-6) M, Bmax,2 = 1473 x 10(-12) mol/mg protein), while pigmented epithelial (PE) membranes have one binding site (Kd = 82 x 10(-9) M, Bmax = 377 x 10(-12) mol/mg protein). The three sites of NPE/PE membranes were found to show the highest affinity for PGE2 by competitive binding assay; affinity for PGF2 alpha and PGD2 was several orders of magnitude less. PGE2 binding to the higher affinity site of NPE membranes induced inhibition of adenylate cyclase activity. Activation of the lower affinity site resulted in activation of the cyclase activity. PGE2 binding to PE membranes caused inhibition of adenylate cyclase activity. There is evidence that cyclic adenosine monophosphate (cAMP) affects transport of ions and water in the ciliary epithelium, hence modulates aqueous humor inflow. The present results, therefore suggest that aqueous humor production by the ciliary NPE cells may be influenced by changes in the concentration of PGE2 which binds to the receptor subtypes having opposing effects on adenylate cyclase and regulates intracellular cAMP level.
Sano
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N
Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201.
Shichi
H
H
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002924:Ciliary Body / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D015232:Dinoprostone / Q000502:physiology*; D004789:Enzyme Activation; D004848:Epithelium / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D015290:Second Messenger Systems; D013552:Swine
D018078:Receptors, Prostaglandin E; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone