Melatonin induces urethral contraction and increases intraurethral pressure via MT1 receptor activation in female rats.

Melatonin is released by the pineal gland and exerts numerous physiological effects via specific G protein-coupled receptors named MT1 and MT2 receptors. It is well known that melatonin acts as a key regulator of circadian rhythm through the activation of these receptors on the central nervous system. However, the expression and function of melatonin receptors in the lower urinary tract remain unclear. This study aimed to investigate the expression and function of melatonin receptors in female urethra. mRNA expression analysis exhibited high expression of MT1 and MT2 receptor mRNA in human and rat female urethra. A study of isolated female rat urethral tissue strips using melatonin receptor agonists and an antagonist strongly revealed that stimulation of melatonin MT1 receptor induced urethral smooth muscle contraction. Further investigation of the mechanism underlying this melatonin MT1 receptor-related urethral contraction demonstrated that stimulation of MT1 receptors in urethra activates intracellular Ca2+ mobilization via Gq protein-dependent pathways, resulting in smooth muscle contraction. In vivo studies also revealed that melatonin receptor agonists induced an increase in urethral perfusion pressure in female rats. This is the first study to clearly demonstrate the expression and function of melatonin receptors in the urethra. These findings suggested that activation of MT1 receptors could be a potential pharmacological target for modulation of urethral function.