Lens beta-adrenergic receptors. Functional coupling to adenylate cyclase and photoaffinity labeling.
Beta-adrenergic drugs affect lens epithelial and fiber cells. The regulation and cellular integration of lens beta-adrenergic responses are largely unknown. These studies further characterize beta-adrenergic receptors in lens cells with respect to cyclic adenosine monophosphate (cAMP) production and identification of receptor polypeptides. Stimulation of beta-adrenergic receptors in organ-cultured chick lenses resulted in dose-dependent increases in intracellular cAMP levels. Isoproterenol-elicited cAMP accumulation was found in both epithelial/superficial fiber cells and cortical fiber cells. Hormonal stimulation also apparently initiated additional mechanisms involved in the regulation of cAMP levels (ie, phosphodiesterase activation/receptor desensitization). Individual receptor polypeptides were identified in epithelial and fiber membranes with the photoaffinity probe 125I-iodocyanopindolol diazarine. The probe specifically labeled distinct populations of receptor polypeptides in the two cell types. Lens beta-adrenergic receptors were also shown to bind (-) stereoisomers of adrenergic ligands preferentially. These results indicate that differentiating fiber cells are hormonally sensitive to beta-adrenergic stimulation and that epithelial and fiber cells may respond differentially to beta-adrenergic drugs, at least in part, because of their distinct receptor polypeptides.
Ireland
M E
ME
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.
Shanbom
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000345:Affinity Labels; D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D046508:Culture Techniques; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D003978:Diazomethane / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D020120:Iodocyanopindolol / Q000031:analogs & derivatives*; D007545:Isoproterenol / Q000494:pharmacology; D007908:Lens, Crystalline / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000345:Affinity Labels; D010455:Peptides; D011943:Receptors, Adrenergic, beta; C058075:iodocyanopindolol diazirine; D003978:Diazomethane; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine