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Abstract #15548 Published in IGR 1-3
Ocular effects of adrenomedullin
Taniguchi T; Kawase K; Gu Z-B; Kimura M; Okano Y; Kawakami H; Tsuji A; Kitazawa YExperimental Eye Research 1999; 69: 467-474
The purpose of this study was to determine the expression and effects of adrenomedullin (AM), a novel vasodilator peptide, in the eye. Expression of AM mRNA was examined in the rat iris-ciliary body using reverse transcription-polymerase chain reaction (RT-PCR). In rabbits, intraocular pressure (IOP) was measured periodically after intravitreal injection (20 &mgr;l) of AM (10-7-10-4 m) into one eye. In separate groups of rabbits, 30 minutes after intravitreal injection of either AM-(22-52) (10-3 m), a specific AM receptor antagonist, or CGRP-(8-37) (10-3 m), a CGRP1 receptor antagonist, into one eye, AM (10-6 m) was injected into both eyes, and IOP was measured. Using different rabbits, aqueous protein and cAMP concentrations were determined six hours after injection of AM. Expression of AM mRNA was detected in the rat iris-ciliary body. In rabbits, intravitreally administered AM (10-6-10-4 m) profoundly lowered IOP, and the maximum effect was observed at four to eight hours. The ocular hypotensive effect of AM was dose-dependent (10-7-10-4 m). Pretreatment with CGRP-(8-37) did not significantly inhibit the ocular hypotensive effect of AM (10-6 m), whereas pretreatment with AM-(22-52) completely abolished it. AM (10-6 m) did not significantly affect aqueous protein concentration. The higher dose of AM (10-5 m) induced a significant increase in aqueous protein, which was not associated with an increase in the aqueous cAMP content and was significantly inhibited by AM-(22-52) and CGRP-(8-37). These results demonstrate that AM is expressed in the iris-ciliary body and decreases IOP mainly via specific AM receptors, and suggest that AM may play a role in controlling IOP.
Dr. T. Taniguchi, Department of Ophthalmology, Gifu University School of Medicine, Gifu; Japan
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)