Pharmacological characterization of beta-adrenoceptor subtype involvement in the ocular hypotensive response to beta-adrenergic stimulation.
The decrease in intraocular pressure elicited by isoproterenol in ocular normotensive animals is widely recognized. The participation of the beta-adrenoceptor subtypes in mediating this ocular hypotensive response has, however, remained unclear, because previous studies have been limited to monitoring the activity of single, supramaximal doses of relatively selective beta 2-adrenoceptor agonists. The studies herein report a relatively extensive pharmacological characterization of beta 1- and beta 2-adrenoceptor involvement in ocular hypotension associated with beta-adrenergic stimulation in the pigmented rabbit. A beta 2-adrenoceptor mechanism was indicated by the following evidence: isoproterenol and relatively selective beta 2-adrenoceptor agonists produced ocular hypotension over a similar dose range (0.001-0.1%; beta 1-adrenoceptor agonists, at doses likely to confer beta 1-adrenoceptor specificity, did not cause a similar decrease in intraocular pressure; the ocular hypotensive response to isoproterenol was abolished by topical timolol and pindolol and the relatively selective beta 2-adrenoceptor antagonist ICI 118551, whereas the relatively selective beta 1-adrenoceptor antagonists metoprolol and betaxolol were topically inactive; intravenous injection of beta 1-adrenoceptor-specific doses of metoprolol and betaxolol had little effect on isoproterenol-induced ocular hypotension, whereas the response was antagonized by a beta 2-adrenoceptor-specific i.v. dose of ICI 118551. These pharmacological results are consistent with radioligand binding and beta-adrenoceptor-linked adenylate cyclase studies which indicate a predominantly beta 2-adrenoceptor population associated with the ocular ciliary processes. None of the beta-blockers themselves altered normal intraocular pressure in the pigmented rabbit.
Woodward
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DF
Chen
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Padillo
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Ruiz
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013997:Time Factors; D013999:Timolol / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D013999:Timolol; D010869:Pindolol; D007545:Isoproterenol