title: Ocular effects of adrenomedullin.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: K
authors.initials: K
authors.lastname: Kawase
authors.forename: Z B
authors.initials: ZB
authors.lastname: Gu
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: Y
authors.initials: Y
authors.lastname: Okano
authors.forename: H
authors.initials: H
authors.lastname: Kawakami
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
authors.forename: Y
authors.initials: Y
authors.lastname: Kitazawa
mesh_terms: 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*
chemical_list: D005136:Eye Proteins; D010455:Peptides; D012333:RNA, Messenger; D014665:Vasodilator Agents; D053607:Adrenomedullin; D000242:Cyclic AMP; D015232:Dinoprostone