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 huma n bladder. Strips of detrusor muscle were contracted by the tachykinin s neurokinin A and neuropeptide gamma, and by the NK2 receptor selecti ve agonists [Lys(5),MeLeu(9),Nle(10)]-NKA(4-10) and [Lys(5),Tyr(I-2)(7 ),MeLeu(9),Nle(10)]-NKA(4-10), with pD(2) values 8.2, 8.0, 8.1 and 7.1 .[Sar(9),Met(O-2)(11)]-SP and senktide were ineffective agonists, indi cating an absence of NK1 and NK3 receptors. The contractile responses to [Lys(5),MeLeu(9),Nle(10)]-NKA(4-10) were inhibited competitively by the NK2 receptor selective antagonists SR 48968, GR 94800 and MDL 299 13, with pA(2) values 9.1, 8.6 and 7.0. Specific binding of the new NK 2 receptor selective radioligand [I-125]-[L ys(5),Tyr(I-2)(7),MeLeu(9) ,Nle(10)]-NKA(4-10) was saturable to a high affinity site (K-D 2.3 nM. ). Specific binding was inhibited by NK2 receptor agonists and antagon ists, but not by NK1 and NK3 analogues, showing binding to NK2 recepto rs only. These data indicate that NK2 receptors may be involved in reg ulation of detrusor contractility in the human bladder.