Carboxypeptidase M-like enzyme modulates the noncholinergic bronchoconstrictor response in guinea pig.
We studied the effects of aerosolized DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid (MGTA) (10(-4) M, 90 breaths), a specific inhibitor of carboxypeptidase B-type enzymes, on changes in total pulmonary resistance (RL) induced by aerosolized capsaicin (10(-7) to 10(-4) M; 10 breaths at each concentration) and vagus nerve stimulation (5 V, 5 ms, for 20 s at frequencies varying from 2 to 10 Hz) in anesthetized, atropinized, and ventilated guinea pigs. We also studied the effect of aerosolized MGTA on the bronchoconstrictor response to either aerosolized substance P, neurokinin A (10(-7) to 10(-4) M; 10 breaths at each concentration), and carbachol (10(-5) to 2 x 10(-4) M; 10 breaths at each concentration) or to i.v. administration of neurokinin A (10(-11) to 10(-8) mol/kg), bradykinin (10(-10) to 10(-7) mol/kg), and histamine (10(-8) to 10(-6) mol/kg). Although aerosolized MGTA caused no change in basal RL (P > 0.5), it did potentiate the noncholinergic bronchoconstrictor response to capsaicin (n = 5; P < 0.001) as well as to vagus nerve stimulation (n = 5; P = 0.001). In contrast, MGTA did not potentiate the bronchoconstrictor response to either aerosolized substance P, neurokinin A, and carbachol or to i.v. administration of neurokinin A, histamine, and bradykinin. Carboxypeptidase activity cleaving C-terminal arginine or lysine was found in the membrane preparations of trachea and lung from guinea pigs. The membrane-bound carboxypeptidase activity was maximal at pH 7.0 and was enhanced by the presence of CoCl2 (1 mM) in both the tracheal and lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Desmazes
N
N
Service de Pneumologie, U.F.R. Cochin-Port-Royal, Université René Descartes, Paris, France.
Lockhart
A
A
Lacroix
H
H
Dusser
D J
DJ
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D016084:Bronchoconstriction; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D058851:GPI-Linked Proteins; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015288:Neurokinin A / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D058851:GPI-Linked Proteins; D011950:Receptors, Cholinergic; D013373:Substance P; C029729:2-mercaptomethyl-3-guanidinoethylthiopropionic acid; D006632:Histamine; D015288:Neurokinin A; D015097:3-Mercaptopropionic Acid; C058479:carboxypeptidase M; D008666:Metalloendopeptidases; D002211:Capsaicin; D001920:Bradykinin