PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs.
Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.
Kanazawa
H
H
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Kamoi
H
H
Kawaguchi
T
T
Shoji
S
S
Fujii
T
T
Kudoh
S
S
Hirata
K
K
Yoshikawa
J
J
D053607:Adrenomedullin; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D016085:Bronchoconstrictor Agents / Q000633:toxicity; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002211:Capsaicin / Q000633:toxicity; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides; D011506:Proteins / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology
D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D053607:Adrenomedullin; D013373:Substance P; D015288:Neurokinin A; D007545:Isoproterenol; D002211:Capsaicin