Calcitonin gene-related peptide antagonizes the protective effect of adrenomedullin on histamine-induced bronchoconstriction.
1. In the present study the possible relationship between adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) in the regulation of airway functions in anaesthetized guinea-pigs was examined in vivo. 2. We found that AM significantly inhibited histamine-induced bronchoconstriction in a dose-dependent manner. CGRP or the CGRP receptor antagonist (CGRP [8-37]) alone did not affect pulmonary resistance and pretreatment with CGRP or CGRP [8-37] did not significantly affect histamine-induced bronchoconstriction. However, AM-induced bronchoprotection was significantly inhibited by pretreatment with CGRP or CGRP [8-37] in a dose-dependent manner. 3. It is therefore possible that CGRP may be competitive, at least in part, with binding sites of AM in the guinea-pig airway. Exogenous AM may be useful for the management of bronchial asthma, not only as a potent bronchodilator, but also as a functional antagonist of CGRP.
Kanazawa
H
H
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Kawaguchi
T
T
Kamoi
H
H
Fujii
T
T
Kudoh
S
S
Hirata
K
K
Kurihara
N
N
Yoshikawa
J
J
D053607:Adrenomedullin; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology*; D008297:Male; D008916:Miotics / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D001993:Bronchodilator Agents; D006633:Histamine Antagonists; D008916:Miotics; D010446:Peptide Fragments; D010455:Peptides; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide