Elucidation of the mechanism whereby prostanoids enhance bladder contractile activity

Summary
It is well established that incidences of urinary disorders, such as overactive bladder (OAB), increases with age in humans. The number of patients suffering from such dysuria is increasing in Japan, a country with a super-aged society. Although drugs that act on the autonomic nervous system have been used to treat OAB, newer, more effective, and safer therapeutic agents are desirable from the perspective of side effects and efficacy. Prostanoids have been identified as possible causes of OAB, and prostanoid receptor antagonists are thus considered to have potential utility as novel therapeutic agents for OAB. However, there has to date been limited information available regarding the effects of different prostanoids on urinary bladder smooth muscle and associated mechanisms of action. Against this background, Professor Yoshio Tanaka and his research group from the Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, examined the effects of different prostanoids on the contractile activity of urinary bladder smooth muscle isolated from guinea pig, and investigated their mechanisms of action both pharmacologically and biochemically. They found that prostanoids enhance the contractile activity of urinary bladder smooth muscle, and that prostanoid TP receptors are among their targets. It was also observed that stimulating TP receptors enhanced urinary bladder contractile function via the activation of multiple Ca²⁺ channels (voltage-gated Ca²⁺ channels and store-operated Ca²⁺ channels). These findings indicate that prostanoids could potentially induce abnormal contractions in urinary bladder smooth muscle, and that TP receptors and Ca²⁺ channels activated by TP receptor stimulation may represent new targets for OAB treatments.