NK1 receptor stimulation causes contraction and inositol phosphate increase in medium-size human isolated bronchi.
Although contraction of human isolated bronchi is mediated mainly by tachykinin NK2 receptors, NK1 receptors, via prostanoid release, contract small-size (approximately 1 mm in diameter) bronchi. Here, we have investigated the presence and biological responses of NK1 receptors in medium-size (2-5 mm in diameter) human isolated bronchi. Specific staining was seen in bronchial sections with an antibody directed against the human NK1 receptor. The selective NK1 receptor agonist, [Sar(9), Met(O2)(11)]SP, contracted about 60% of human isolated bronchial rings. This effect was reduced by two different NK1 receptor antagonists, CP-99,994 and SR 140333. Contraction induced by [Sar(9), Met(O2)(11)]SP was independent of acetylcholine and histamine release and epithelium removal, and was not affected by nitric oxide synthase and cyclooxygenase (COX) inhibition. [Sar(9), Met(O2)(11)]SP increased inositol phosphate (IP) levels, and SR 140333 blocked this increase, in segments of medium- and small-size (approximately 1 mm in diameter) human bronchi. COX inhibition blocked the IP increase induced by [Sar(9), Met(O2)(11)]SP in small-size, but not in medium-size, bronchi. NK1 receptors mediated bronchoconstriction in a large proportion of medium-size human bronchi. Unlike small-size bronchi this effect is independent of prostanoid release, and the results are suggestive of a direct activation of smooth muscle receptors and IP release.
Amadesi
S
S
Pharmacology Unit, Department of Experimental and Clinical Medicine, University of Ferrara, Italy.
Moreau
J
J
Tognetto
M
M
Springer
J
J
Trevisani
M
M
Naline
E
E
Advenier
C
C
Fisher
A
A
Vinci
D
D
Mapp
C
C
Miotto
D
D
Cavallesco
G
G
Geppetti
P
P
D000704:Analysis of Variance; D001980:Bronchi / Q000276:immunology / Q000378:metabolism*; D016084:Bronchoconstriction / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D009130:Muscle, Smooth / Q000276:immunology; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000502:physiology*
D007295:Inositol Phosphates; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1