Journal of Applied Physiology, Vol 78, Issue 4 1234-1241, Copyright © 1995 by American Physiological Society

ARTICLES

Substance P-induced histamine release in tracheally perfused guinea pig lungs

C. M. Lilly, A. E. Hall, I. W. Rodger, L. Kobzik, K. J. Haley and J. M. Drazen
Department of Medicine, Beth Israel Hospital, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

The capacity of substance P (SP) and endogenously released tachykinins to liberate histamine was examined in isolated tracheally perfused guinea pig lungs. Increasing doses of tracheally injected SP were associated with the recovery of increasing amounts of histamine from lung effluent. The mechanism of SP-induced histamine liberation was explored in studies with neurokinin-(NK) receptor agonists and antagonists. Tracheal injection of either the NK1 agonist [Sar9,Met(O2)11]SP or the NK2 agonist [beta-Ala8]-neurokinin A-(4-10) was associated with a significant increase in histamine recovery from lung effluent. In addition, both the NK1 antagonist CP-99994 and the NK2 antagonist SR-48968 significantly inhibited SP-induced histamine release. These findings support the hypothesis that SP can liberate histamine from guinea pigs lungs by a mechanism that depends predominantly on NK1- and NK2-receptor activation. The liberation of endogenous tachykinins by acute tracheal injection of capsaicin was also associated with augmented histamine recovery, which was inhibited by combined NK1- and NK2-receptor blockade. Tracheal injection of SP was associated with an increase in the percentage of airway mast cells exhibiting histological evidence of degranulation. This study demonstrates that exogenous SP, as well as endogenous tachykinins released from capsaicin-sensitive neurons, can liberate histamine, most likely from airway mast cells, by a mechanism that depends predominantly on the activation of NK1 and NK2 receptors.

This article has been cited by other articles:

				D. R. Bergren Prostaglandin involvement in lung C-fiber activation by substance P in guinea pigs J Appl Physiol, June 1, 2006; 100(6): 1918 - 1927. [Abstract] [Full Text] [PDF]

				R. Saban, N. P. Gerard, M. R. Saban, N.-B. Nguyen, D. J. DeBoer, and B. K. Wershil Mast cells mediate substance P-induced bladder inflammation through an NK1 receptor-independent mechanism Am J Physiol Renal Physiol, October 1, 2002; 283(4): F616 - F629. [Abstract] [Full Text] [PDF]

				K. J. Haley, M. E. Sunday, R. Osathanondh, J. Du, C. Vathanaprida, V. V. Karpitsky, J. E. Krause, and C. M. Lilly Developmental expression of neurokinin A and functional neurokinin-2 receptors in lung Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1348 - L1358. [Abstract] [Full Text] [PDF]

				T. Cao, N. P. Gerard, and S. D. Brain Use of NK1 knockout mice to analyze substance P-induced edema formation Am J Physiol Regulatory Integrative Comp Physiol, August 1, 1999; 277(2): R476 - R481. [Abstract] [Full Text] [PDF]

				M. SCHUILING, A. B. ZUIDHOF, J. ZAAGSMA, and H. MEURS Involvement of Tachykinin NK1 Receptor in the Development of Allergen-induced Airway Hyperreactivity and Airway Inflammation in Conscious, Unrestrained Guinea Pigs Am. J. Respir. Crit. Care Med., February 1, 1999; 159(2): 423 - 430. [Abstract] [Full Text]