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Abstract #15549 Published in IGR 1-3

Biphasic intraocular pressure response to calcitonin gene-related peptide

Taniguchi T; Nakai Y; Karim Z; Gu Z-B; Kawase K; Kitazawa Y
Current Eye Research 1999; 5: 432-438


PURPOSE: To examine the effects of calcitonin gene-related peptide (CGRP) on intraocular pressure (IOP). METHODS: IOP was periodically measured in rabbits treated with intravitreal injection (20 æl) of either: (1) CGRP (10-4~10-7 M) into one eye; (2) CGRP (10-4 or 10-6 M) into both eyes, 30 minutes after intravitreal administration of CGRP-(8-37) (10-3 M), a CGRP1 receptor antagonist, into one eye; (3) CGRP (10-4 or 10-6 M) into one eye, 30 minutes after intravenous administration (200 mg/kg) of either Nw-nitro-L-arginine methyl ester (L-NAME), a nonselective inhibitor of nitric oxide synthase (NOS), or aminoguanidine (AG), a selective inhibitor of inducible NOS; or (4) CGRP (10-4 or 10-6 M) into one eye together with intraperitoneal indomethacin (50 mg/kg at -1 and 4 hour). RESULTS: CGRP (10-4 and 10-5 M) produced a biphasic IOP response, which consisted of an early ocular hypertensive phase and a subsequent sustained hypotensive phase, while CGRP (10-6 M) yielded only a profound IOP reduction. CGRP-(8-37) significantly inhibited the IOP elevation induced by CGRP (10-4 M), and completely abolished the IOP reduction induced by CGRP (10-6 M). The IOP increase induced by CGRP (10-4 M) was completely abolished by L-NAME, but not affected by AG. The IOP reduction induced by CGRP (10-6 M) was not affected by L-NAME. Indomethacin did not significantly affect the IOP responses to CGRP. CONCLUSIONS: CGRP dose-dependently produces a biphasic IOP response, which is mediated by CGRP1 receptors. It is suggested that constitutive NOS is involved in the early ocular hypertensive response.

Dr. T. Taniguchi, Gifu University School of Medicine, Department of Ophthalmology, Gifu; Japan


Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)



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