Neurokinin (NK2) receptors mediate nonadrenergic noncholinergic contractile responses to electrical stimulation and resiniferatoxin in guinea pig trachea.

In the present study we characterized the receptor(s) that mediates non-adrenergic non-cholinergic (NANC) contractions of isolated guinea pig cervical trachea, using CP-99,994, a selective neurokinin (NK1) receptor antagonist, and SR-48,968, a selective neurokinin (NK2) receptor antagonist. The activity of these two antagonists was determined against contractions to the selective agonists ([βAla8]NKA(4–10) for NK2 and [Sar9,Met(O2)11]SP for NK1) and the nonselective (SP and NKA) NK receptor agonists. CP-99,994 was inactive versus NKA and [βAla8]NKA(4–10) but antagonized SP- and [Sar9,Met(O2)11]SP-induced contractions with −log KB values of 5.6 ± 0.2 and 7.7 ± 0.2, respectively. SR-48,968 was inactive versus SP and [Sar9,Met(O2)11]SP but was active versus NKA and [βAla8]NKA(4–10), yielding −log KB values of 8.4 ± 0.2 and 9.1 ± 0.2, respectively. In the presence of 1 μM atropine, 1.4 μM indomethacin, 0.2 μM timolol, and 4 μM thiorphan, electrical field stimulation (16 Hz, 2.0 ms, 50 V for 10 every 30 min) e...