Adrenomedullin and proadrenomedullin N-terminal 20 peptide induce histamine release from rat peritoneal mast cell.
Adrenomedullin (ADM)-induced histamine release from rat peritoneal mast cells was investigated. We compared the ability of full-length ADM to induce histamine release to the fragments ADM-(1-25) and ADM-(22-52), as well as proadrenomedullin N-terminal 20 peptide (PAMP). ADM (10(-8) to 10(-5) M) and PAMP (10(-8) to 10(-5) M) dose-dependently increased histamine release from peritoneal mast cell preparations. The effect of ADM-(1-25) was similar to ADM, whereas ADM-(22-52) did not show any effects. These data suggest the relative importance of the ADM C-terminal fragment, which contains a six-membered ring structure. Histamine release, induced by ADM, was significantly and dose-dependently inhibited by the addition of ADM-(22-52) (10(-5) M), Ca(2+) (0.5 to 2.0 mM), and benzalkonium chloride (3 to 7 microM), a selective inhibitor of Gi type G proteins. In contrast, PAMP (10(-5) M)-induced histamine release was not inhibited by Ca(2+). These results suggest that ADM induce histamine release via a putative ADM receptor in a manner sensitive to Gi-protein function and extracellular Ca(2+) concentration, and that PAMP might produce its effect by a different mechanism than ADM.
Yoshida
M
M
Internal Medicine II, Nagoya University School of Medicine, 65 Tsuruma-Cho, Nagoya 466-8550, Showa, Japan.
Yoshida
H
H
Kitaichi
K
K
Hiramatsu
K
K
Kimura
T
T
Ito
Y
Y
Kume
H
H
Yamaki
K
K
Suzuki
R
R
Shibata
E
E
Hasegawa
T
T
Takagi
K
K
D053607:Adrenomedullin; D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors; D006636:Histamine Release / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D010529:Peritoneal Cavity / Q000166:cytology*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D001548:Benzalkonium Compounds; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; C104782:adrenomedullin (22-52); D053607:Adrenomedullin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium