Developmental expression of neurokinin A and functional neurokinin-2 receptors in lung.
Peribronchial smooth muscle constriction causes airway stretch, an important mechanical force in developing lung. Little is known about factors influencing these spontaneously active muscle elements. We measured contractile activity of neurokinin (NK) receptors on fetal intrapulmonary smooth muscle by tracheal perfusion assay (n = 11). Injecting either capsaicin or the NK(2) receptor agonist [NLE(10)]NKA resulted in significant (P < 0.05) bronchoconstriction. A specific NK(2) receptor antagonist inhibited constriction caused by endogenous tachykinins released by capsaicin. We then examined NK(2) receptor (n = 44) and NKA (n = 23) ontogeny in human lung. NKA immunostaining was identified in peribronchial nerves in samples with gestational age >12 wk. NK(2) receptor protein was identified in peribronchial and perivascular smooth muscle. These results indicate that endogenous tachykinins released by the developing lung act via NK(2) receptors to cause smooth muscle constriction. We speculate that tachykinins could modulate lung development.
Haley
K J
KJ
Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Sunday
M E
ME
Osathanondh
R
R
Du
J
J
Vathanaprida
C
C
Karpitsky
V V
VV
Krause
J E
JE
Lilly
C M
CM
D000328:Adult; D017609:Barium Compounds / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D016210:Methacholine Chloride / Q000494:pharmacology; D009130:Muscle, Smooth / Q000196:embryology / Q000294:innervation / Q000378:metabolism; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010477:Perfusion; D012333:RNA, Messenger / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000098:blood supply / Q000187:drug effects / Q000196:embryology / Q000378:metabolism
D017609:Barium Compounds; D016085:Bronchoconstrictor Agents; D002712:Chlorides; D010455:Peptides; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C024986:barium chloride; D016210:Methacholine Chloride; D015288:Neurokinin A; D002211:Capsaicin