NK2 receptor mediated detrusor muscle contraction involves Gq/11-dependent activation of voltage-dependent calcium channels and the RhoA-Rho kinase pathway.

NK2 receptor mediated detrusor muscle contraction involves Gq/11-dependent activation of voltage-dependent calcium channels and the RhoA-Rho kinase pathway. Am J Physiol Renal Physiol. 2019 Aug 28;: Authors: Dér B, Molnár PJ, Ruisanchez É, Őrsy P, Kerék M, Faragó B, Nyirády P, Offermanns S, Benyó Z Abstract Tachykinins (TKs) are involved both in the physiological regulation of urinary bladder functions and in the development of overactive bladder (OAB) syndrome. The aim of the present study was to investigate the signal transduction pathways of TKs in the detrusor muscle to provide potential pharmacological targets for the treatment of bladder dysfunctions related to enhanced TK production. Contraction force, intracellular Ca2+ concentration([Ca2+]ic) and RhoA activity were measured in mouse urinary bladder smooth muscle (UBSM). TKs and the NK2 receptor (NK2R) specific agonist [β-Ala⁸]-NKA(4-10) evoked contraction, which was inhibited by the NKR2 antagonist MEN10376. In Gαq/11 deficient mice [β-Ala⁸]-NKA(4-10)-induced contraction and [Ca2+]ic increase were abolished. Although Gq/11-proteins are linked principally to phospholipase C β (PLC-β) and inositol trisphosphate-mediated Ca2+ release from intracellular stores, we found that PLC-β inhibition and sarcoplasmic reticulum Ca2+ depletion failed to have any effect on contraction induced by [β-Ala⁸]-NKA(4-10). In contrast, lack of extracellular Ca2+ or blockade of ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research