Biphasic intraocular pressure response to calcitonin gene-related peptide.
OBJECTIVE
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 ael) of either: 1) CGRP (10(-4) approximately 10(-7) M) into one eye; 2) CGRP (10(-4) or 10(-6) M) into both eyes 30 min 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 min 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 along with intraperitoneal indomethacin (50 mg/ kg at -1 and 4 h).


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.
Taniguchi
T
T
Gifu University School of Medicine, Department of Ophthalmology, Gifu, Japan. tani-gif@umin.u-tokyo.ac.jp
Nakai
Y
Y
Karim
Z
Z
Gu
Z B
ZB
Kawase
K
K
Kitazawa
Y
Y
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005136:Eye Proteins; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin