Ocular alpha 2-receptor subclasses and antiglaucoma efficacy.
An overview of the ocular hypotensive actions of some alpha 2-agonists with imidazoline structures is presented. These agents inhibit isoproterenol-stimulated adenylate cyclase (AC) activity in ciliary process membrane through a Na+ and GTP-dependent mechanism. Receptor binding studies with the alpha 2-agonist radioligand [125I] p-iodoclonidine ([125I]PIC) in rabbit ciliary body membranes indicate that the alpha 2-receptor subtype is alpha 2A. Gpp(NH)p and NaCl dose-dependently decreased the number of [125I]PIC binding sites by shifting the receptor-G protein complexes from the high affinity state to the low affinity state for agonist binding. This is consistent with the observations that inhibition of AC was Na+ and GTP dependent. The NaCl and Gpp(NH)p effects on binding appeared to be through different mechanisms. The alpha 2-receptor in ciliary process thus appears to be an alpha 2A-receptor that is negatively coupled to the AC-cAMP generating system.
Jin
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North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth.
Gooding
J R
JR
Yorio
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T
D000262:Adenylyl Cyclases / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005901:Glaucoma / Q000188:drug therapy*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism / Q000627:therapeutic use; D007429:Intraocular Pressure; D008297:Male; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification* / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; D006165:Guanylyl Imidodiphosphate; D012965:Sodium Chloride; D000262:Adenylyl Cyclases