Characterization of tachykinin NK2 receptors in human urinary bladder.

Functional and radioligand binding studies with selective agonists and antagonists were used to investigate tachykinin receptors in the human bladder. Strips of detrusor muscle were contracted by the tachykinins neurokinin A and neuropeptide gamma, and by the NK2 receptor selective agonists [Lys5,MeLeu9,Nle10]-NKA(4-10) and [Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4- 10), with pD2 values 8.2, 8.0, 8.1 and 7.1. [Sar9,Met(O2)11]-SP and senktide were ineffective agonists, indicating an absence of NK1 and NK3 receptors. The contractile responses to [Lys5,MeLeu9,Nle10]-NKA(4-10) were inhibited competitively by the NK2 receptor selective antagonists SR 48968, GR 94800 and MDL 29913, with pA2 values 9.1, 8.6 and 7.0. Specific binding of the new NK2 receptor selective radioligand [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10) was saturable to a high affinity site (KD 2.3 nM.). Specific binding was inhibited by NK2 receptor agonists and antagonists, but not by NK1 and NK3 analogues, showing binding to NK2 receptors only. These data indicate that NK2 receptors may be involved in regulation of detrusor contractility in the human bladder.