Substance P and neurokinin-1 receptor expression by intrinsic airway neurons in the rat.
Tachykinins and their receptors are involved in the amplification of inflammation in the airways. We analyzed the expression of preprotachykinin-A (PPT-A) and neurokinin-1 (NK-1) receptor genes by intrinsic airway neurons in the rat. We also tested the hypothesis that PPT-A-encoded peptides released by these neurons fulfill the requisite role of substance P in immune complex injury of the lungs. We found that ganglion neurons in intact and denervated airways or in primary culture coexpress PPT-A and NK-1 receptor mRNAs and their protein products. Denervated ganglia from tracheal xenografts (nu/nu mice) or syngeneic lung grafts had increased PPT-A mRNA contents, suggesting preganglionic regulation. Formation of immune complexes in the airways induced comparable inflammatory injuries in syngeneic lung grafts, which lack peptidergic sensory fibers, and control lungs. The injury was attenuated in both cases by pretreatment with the NK-1 receptor antagonist LY-306740. We conclude that tachykinins released by ganglia act as a paracrine or autocrine signal in the airways and may contribute to NK-1 receptor-mediated amplification of immune injury in the lungs.
Fontán
J J
JJ
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. FONTAN@KIDS.WUSTL.EDU
Cortright
D N
DN
Krause
J E
JE
Velloff
C R
CR
Karpitskyi
V V
VV
Carver
T W
TW
Shapiro
S D
SD
Mora
B N
BN
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D002478:Cells, Cultured; D003714:Denervation; D005724:Ganglia / Q000378:metabolism; D008168:Lung / Q000294:innervation / Q000378:metabolism; D016040:Lung Transplantation; D051379:Mice; D008819:Mice, Nude; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000378:metabolism*; D011014:Pneumonia / Q000276:immunology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism; D014132:Trachea / Q000294:innervation* / Q000637:transplantation; D014183:Transplantation, Heterologous; D014185:Transplantation, Isogeneic
D000081:Acetamides; D000936:Antigen-Antibody Complex; C102280:LY 306740; D064729:Neurokinin-1 Receptor Antagonists; D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C044206:preprotachykinin