Moxonidine-induced inhibition of norepinephrine release in monkey and rabbit ciliary bodies: role of cGMP.
This study was designed to determine whether in isolated rabbits iris-ciliary bodies and monkey ciliary bodies, cGMP plays a role in the action of moxonidine, an alpha 2- and imidazoline (I1) receptor agonist. In field-stimulated rabbit iris-ciliary bodies, dose-related inhibition of norepinephrine release was induced by 8-Br-cGMP, moxonidine or sodium nitroprusside; 8-Br-cGMP in combination with moxonidine did not enhance inhibition of norepinephrine release. Sodium nitroprusside at intermediate and high concentrations stimulated cGMP production in rabbit iris-ciliary bodies, whereas moxonidine stimulated cGMP production modestly only at a high concentration. When iris-ciliary bodies were pretreated with a low concentration of moxonidine, sodium nitroprusside-stimulated cGMP production was enhanced from 1.6 to 2.2 pmol/mg protein. In field-stimulated monkey ciliary bodies, both sodium nitroprusside and moxonidine inhibited norepinephrine release. Pretreatment of electrically stimulated monkey ciliary bodies with sodium nitroprusside enhanced the suppressive effect of moxonidine on norepinephrine release. In monkey ciliary bodies, moxonidine raised cGMP production more than sodium nitroprusside did, but there was no synergism in cGMP production by combined treatment with moxonidine and sodium nitroprusside. These results suggest that cGMP could play a role in the ocular action(s) of moxonidine in ciliary bodies; however, involvement of cGMP in the action of moxonidine in monkey ciliary bodies seems to be more pronounced than in rabbit iris-ciliary bodies.
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Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, GA 30310-1495, USA.
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002924:Ciliary Body / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000502:physiology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008254:Macaca nemestrina; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits
D000959:Antihypertensive Agents; D007093:Imidazoles; D009599:Nitroprusside; C043482:moxonidine; D006152:Cyclic GMP; D009638:Norepinephrine