Release of tachykinins by histamine, methacholine, PAF, LTD4, and substance P from guinea pig lungs.
The release of substance P- and neurokinin A-like immunoreactivities (SP-LI and NKA-LI) after tracheal infusion of histamine, methacholine, leukotriene D4, and platelet-activating factor was measured in isolated guinea pig lungs superfused through the trachea. Infusion of each of these agonists was associated with a significant (P less than 0.05) increase in the recovery of both SP-LI and NKA-LI from lung perfusates compared with preinfusion baseline recoveries of these peptides. After infusion of bronchoactive mediators, approximately 4-15 times more NKA-LI than SP-LI was recovered from the lung superfusate. Coincident with the release of neuropeptides, mediator infusion was accompanied by an increase in airway opening pressure (Pao). Addition to the perfusate of the neutral endopeptidase inhibitor thiorphan, 1 microM increased the change in Pao induced by histamine (10(-8) mol, P less than 0.005) and methacholine (10(-8) mol, P less than 0.02) and increased the recovery of NKA-LI (P less than 0.05 for histamine and methacholine). Addition of isoproterenol to the perfusion buffer reduced, but did not abolish, either the Pao response or the increased recovery of NKA-LI (P less than 0.05) observed after histamine infusion. We conclude that bronchoactive agonists have the capacity to release both SP-LI and NKA-LI, and we speculate that NKA contributes to the bronchomotor response observed in response to histamine or methacholine.
Martins
M A
MA
Department of Medicine, Beth Israel Hospital, Boston, Massachusetts.
Shore
S A
SA
Drazen
J M
JM
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000502:physiology*; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015288:Neurokinin A / Q000378:metabolism; D010972:Platelet Activating Factor / Q000502:physiology*; D013189:SRS-A / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism / Q000502:physiology*; D015320:Tachykinins / Q000378:metabolism*
D010972:Platelet Activating Factor; D013189:SRS-A; D015320:Tachykinins; D016210:Methacholine Chloride; D013373:Substance P; D006632:Histamine; D015288:Neurokinin A; D015260:Neprilysin