Ocular effects of adrenomedullin.
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 microl) of AM (10(-7)-10(-4)m) into one eye. In separate groups of rabbits, 30 min 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 6 hr 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 4-8 h. 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.
Taniguchi
T
T
Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
Kawase
K
K
Gu
Z B
ZB
Kimura
M
M
Okano
Y
Y
Kawakami
H
H
Tsuji
A
A
Kitazawa
Y
Y
D053607:Adrenomedullin; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005123:Eye / Q000187:drug effects*; D005136:Eye Proteins / Q000378:metabolism; D015870:Gene Expression; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D010455:Peptides / Q000494:pharmacology* / Q000502:physiology; D011680:Pupil / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014665:Vasodilator Agents / Q000494:pharmacology*
D005136:Eye Proteins; D010455:Peptides; D012333:RNA, Messenger; D014665:Vasodilator Agents; D053607:Adrenomedullin; D000242:Cyclic AMP; D015232:Dinoprostone