Modulation of urinary frequency via type 1 lysophosphatidic acid receptors: effect of the novel antagonist ASP6432 in conscious rats.

Modulation of urinary frequency via type 1 lysophosphatidic acid receptors: effect of the novel antagonist ASP6432 in conscious rats. Eur J Pharmacol. 2019 Mar 07;: Authors: Sakamoto K, Noguchi Y, Ueshima K, Ohtake A, Sato S, Imazumi K, Takeda M, Masuda N Abstract Bladder dysfunctions associated with benign prostatic hyperplasia are not sufficiently alleviated by current pharmacotherapies. Lysophosphatidic acid (LPA) is a phospholipid with diverse biological effects. LPA modulates prostate and urethral contraction via the type 1 LPA (LPA1) receptor, suggesting the potential of the LPA1 receptor as a therapeutic target. However, the role of LPA and the LPA1 receptor in bladder function has not been studied in vivo. We investigated the effects of LPA and the novel LPA1 receptor antagonist ASP6432 (potassium 1-(2-{[3,5-dimethoxy-4-methyl-N-(3-phenylpropyl)benzamido]methyl}-1,3-thiazole-4-carbonyl)-3-ethyl-2,2-dioxo-2λ6-diazathian-1-ide) on the micturition reflex in conscious rats using cystometry. Intravenous infusion of LPA decreased the micturition interval and threshold pressure with no apparent changes in baseline pressure or maximum intravesical pressure. ASP6432 inhibited the LPA-induced decrease in MI. In contrast, ASP6432 had no effect on the LPA-induced decrease in threshold pressure. Similarly, ASP6432 had no effect on either baseline pressure or maximum intravesical pressure. We also evaluated the effect of ASP6432 on the ur...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research