PT  - JOURNAL ARTICLE
AU  - Jeremy Mark Hernandez
AU  - Gerard Cox
AU  - Luke Jeffrey Janssen
TI  - Involvement of the Neurokinin-2 Receptor in Airway Smooth Muscle Stretch-Activated Contractions Assessed in Perfused Intact Bovine Bronchial Segments
AID  - 10.1124/jpet.108.141176
DP  - 2008 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 503--510
VI  - 327
IP  - 2
4099  - http://jpet.aspetjournals.org/content/327/2/503.short
4100  - http://jpet.aspetjournals.org/content/327/2/503.full
SO  - J Pharmacol Exp Ther2008 Nov 01; 327
AB  - The airway response to deep inspirations (DIs) in asthmatics has been shown to be ineffective in producing bronchodilation and can even cause bronchoconstriction. However, the manner by which a DI is able to cause bronchoconstriction remains ambiguous. We sought to investigate the pathway involved in this stretch-activated contraction and whether this contraction is intrinsic to airway smooth muscle (ASM). In brief, intact bovine bronchial segments were dissected, and side branches were ligated and then mounted horizontally in an organ bath. Intraluminal pressure was measured under isovolumic conditions. Instantaneously opening and then closing the tap on a column of fluid 5 to 30 cm high evoked a sudden increase in intraluminal pressure (equivalent to the height of the column of fluid) followed by a stress relaxation response of the ASM. When tissues were stimulated with carbachol (10-8 M) or serotonin (10-7 M) for 10 min, and the consequent agonist-evoked pressure response was dissipated manually, the response to the same transmural stretch was accompanied by a slowly developing and prolonged increase in intraluminal pressure. This stretch-activated response was significantly diminished by the stretch-activated cation channel blocker gadolinium (10-3 M), the L-type Ca2+ channel blockers nifedipine (2 × 10-6 M), diltiazem (10-5 M), and verapamil (10-5 M), the sensory neurotoxin capsaicin (10-5 M), and the neurokinin (NK)2 receptor antagonists MEN 10376 ([TyrI,d-Trp6,8,9,Lys10]-NKA(4–10)) (10-5 M) and SR48968 (N-[(2S)-4-(4-acetamido-4-phenylpiperidin-1-yl)-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide) (3 × 10-6 M). These results show the ability of isolated airways to exhibit stretch-activated contractions and suggest a role for stretch-activated cation channels, sensory afferent neurons, the neurotransmitter NKA, and L-type Ca2+ channels in these isolated airway responses. The American Society for Pharmacology and Experimental Therapeutics