Characterization of Tachykinin NK sub 2 Receptors in Human Urinary Bladder

Abstract

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.

Researching bladder afferents—determining the effects of β3‐adrenergic receptor agonists and botulinum toxin type‐A

“…In rodents, NK 1 and NK 2 receptors are located on detrusor smooth muscle, and NK 2 receptors are located on afferent nerve terminals 45. In humans, NK 1 receptors are on afferent terminals and NK 2 receptors are on muscle 45, 46. This same approach can be used to test the effect of β 3 ‐receptor agonists on neuropeptide release, only the drug must be bath applied and will affect the whole sheet preparation (not shown).…”

Tachykinin receptors in guinea-pig airways: characterization using selective ligands

“…This may be attributed to the highly selective nature of this NK2 agonist and to the observation that NK2 binding sites are found on airway smooth muscle only, in the guinea-pig (Strigas and Burcher 1994). Although a similar excellent correlation was also observed at human bladder NK2 receptors (Zeng et al 1995), too much importance, perhaps, should not be made of this correlation, since in both cases only a small number of antagonists were used. There are pitfalls in attempting to compare results of binding and functional studies.…”

Potential therapeutic targets for treatment of the overactive bladder

“…Both NK-1 and NK-2 receptors have been demonstrated in the detrusor muscle of the rat [31] and guinea pig [9]. However, tachykinininduced contraction has been shown to be mediated only by the NK-2 receptor subtype in human detrusor muscle [32,56].…”