Neurokinin receptors subserving plasma extravasation in guinea pig airways.
In the respiratory system the tachykinins substance P and neurokinin A exhibit a variety of effects on airway function that include bronchoconstriction, vasodilatation, and plasma extravasation. Increased microvascular permeability with accompanying plasma extravasation is a principal cause of tissue edema observed in asthma. In guinea pig airways it has been suggested that neurogenic plasma extravasation is mediated by tachykinins, released from sensory nerve terminals, acting via neurokinin (NK) receptors. We have characterized NK receptor mediated plasma extravasation in guinea pig airways, using 125I-labelled human fibrinogen as a marker for leakage. Extravasation was induced using selective NK1 and NK2 receptor agonists, capsaicin, or nonadrenergic, noncholinergic nerve stimulation. The inhibitory effects of the selective nonpeptide NK receptor antagonists (CP 99,994 for NI1 and SR 48,968 for NK2) were also examined. Results from our studies demonstrate conclusively that only NK1 receptors subserve plasma extravasation in the trachea and large airways of the guinea pig. In start contrast, extravasation in the lower airways (secondary bronchi and intraparenchymal airways) of the guinea pig is mediated by both NK1 and NK2 receptors.
Rodger
I W
IW
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, QC, Canada.
Tousignant
C
C
Young
D
D
Savoie
C
C
Chan
C C
CC
D000818:Animals; D002199:Capillary Permeability; D005340:Fibrinogen / Q000378:metabolism; D006168:Guinea Pigs; D008168:Lung / Q000294:innervation; D010880:Piperidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000502:physiology*; D012709:Serum Albumin / Q000378:metabolism
D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D012709:Serum Albumin; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D005340:Fibrinogen