Relaxant effect of adrenomedullin on bovine isolated iris sphincter muscle under resting conditions.
1. The mechanisms involved in the fine adjustment of iris sphincter muscle tone are largely unknown. The aim of the present study was to clarify the effects of adrenomedullin on the resting tension of the bovine isolated iris sphincter muscle. 2. The motor activity of the bovine isolated iris sphincter muscle was measured isometrically. The effects of adrenomedullin on resting tension were analysed in the presence of indomethacin. The presence of adrenomedullin mRNA in the preparation was determined by reverse transcription-polymerase chain reaction. Immunolabelling for adrenomedullin was also performed. 3. Adrenomedullin significantly decreased the resting tension of the muscle. The relaxant effect of adrenomedullin was significantly inhibited by adrenomedullin (22-52), a putative antagonist for the adrenomedullin receptor, or calcitonin gene-related peptide (CGRP) (8-37), a putative antagonist for the CGRP1 receptor. The relaxant effect was almost completely blocked by a combination of adrenomedullin (22-52) and CGRP (8-37). 4. The relaxant effect of adrenomedullin was also significantly diminished by 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthesis, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase. 5. Reverse transcription-polymerase chain reaction analysis showed that adrenomedullin mRNA was expressed in the muscle strip. Immunopositive staining for adrenomedullin was detected in blood vessel cells and in the iris sphincter muscle cells. 6. These results suggest that adrenomedullin may be an autocrine and paracrine regulator of the resting tension of the iris sphincter muscle. Its biological effects may be due to the direct involvement of adrenomedullin receptors and also to the stimulation of CGRP1 receptors. The stimulation of these receptors by the peptide leads to the activation of adenylate cyclase and soluble guanylate cyclase and subsequent relaxation of the muscle strip.
Uchikawa
Y
Y
Department of Orthoptics and Visual Sciences, School of Health Sciences, Kyushu University of Health and Welfare, Miyazaki, Japan.
Okano
M
M
Sawada
A
A
Asada
Y
Y
Kobayashi
H
H
Wada
A
A
Nao-i
N
N
Ohkura
M
M
Tanaka
N
N
Yamamoto
R
R
D053607:Adrenomedullin; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002417:Cattle; D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D019335:Nitroarginine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D015398:Signal Transduction
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D010446:Peptide Fragments; D010455:Peptides; D011810:Quinoxalines; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D019335:Nitroarginine; D016048:Dideoxyadenosine; C021008:2',5'-dideoxyadenosine; D015740:Calcitonin Gene-Related Peptide; D007213:Indomethacin