Adrenomedullin increases phosphatidylcholine secretion in rat type II pneumocytes.
Adrenomedullin, a novel hypotensive peptide, has been reported to be produced in the lung as well as in the adrenal medulla. However, the effect of adrenomedullin on lung function is still poorly understood. In this study, we detected the expression of both adrenomedullin mRNA and putative adrenomedullin receptor mRNA in primary cultures of rat type II pneumocytes. Adrenomedullin increased the secretion of phosphatidylcholine, the predominant component of pulmonary surfactant, by type II pneumocytes. The increase was partly inhibited by pretreatment with the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37). Furthermore, the increased phosphatidylcholine secretion was significantly inhibited by several protein kinase C inhibitors, such as sphingosine, 2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]3-(1H-indol-3-yl) maleimide (Gö6983), 3-[1-(3-amidinothio)-propyl-1H-indoyl-3-yl]3-(1-methyl-1H-++ +indoyl-3-yl ) maleimide methane sulfonate (Ro-31-8220), and staurosporine. Our results suggest that adrenomedullin can be considered a candidate autocrine modulator of surfactant secretion in type II pneumocytes.
Okumura
M
M
Department of Pharmacy, Miyazaki Medical College, 5200 Kihara, Kiyotake-cho, 889-1692, Miyazaki, Japan. okmura@post1.miyazaki-med.ac.jp
Kai
H
H
Arimori
K
K
Iwakiri
T
T
Hidaka
M
M
Shiramoto
S
S
Isohama
Y
Y
Miyata
T
T
D053607:Adrenomedullin; D000818:Animals; D001993:Bronchodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001993:Bronchodilator Agents; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; D010455:Peptides; D010713:Phosphatidylcholines; D012333:RNA, Messenger; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide