ASP6432, a type 1 lysophosphatidic acid receptor antagonist, reduces urethral function during urine voiding and...

Area of Science:

• Pharmacology
• Urology
• Physiology

Background:

• Current treatments for voiding dysfunctions require improvement.
• Lysophosphatidic acid (LPA) contracts the urethra via LPA1 receptors, but their role in voiding is unknown.

Purpose of the Study:

• To investigate the role of LPA1 in regulating urethral tonus during urine voiding.
• To evaluate the efficacy of the LPA1 antagonist ASP6432 and tamsulosin in a rat model of voiding dysfunction.

Main Methods:

• Administered ASP6432 and tamsulosin to anesthetized rats to measure urethral perfusion pressure (UPP).
• Assessed voiding function (post-void residual urine and voiding efficiency) in conscious rats using cystometry after inducing dysfunction with L-NAME.

Main Results:

• ASP6432 dose-dependently decreased both baseline and nadir UPP, while tamsulosin only reduced baseline UPP.
• ASP6432 ameliorated L-NAME-induced increases in post-void residual urine and decreases in voiding efficiency, unlike tamsulosin.
• ASP6432 specifically reduced nadir UPP and improved voiding function, effects not observed with tamsulosin.

Conclusions:

• LPA1 plays a significant role in regulating urethral tonus during urine voiding.
• ASP6432 demonstrates potential for improving voiding dysfunctions associated with lower urinary tract diseases.