This article reviewed the results of studies done on animals that assessed effects of melatonin on bladder function. Melatonin does not change strip relaxation on its own. However, pre-treatment with melatonin decreases contractile responses induced by phenylephrine, acetylcholine, bethanechol and KCl in a dose-dependent manner. The contractile responses induced by the direct calcium channel openers are significantly decreased by melatonin pre-treatment. It also binds to Ca2+-activated calmodulin, and prevents it from activating myosin light-chain kinase. It may have direct effects on ion channels which are responsible for regulating bladder contraction. Its other mode of action on bladder occurs via the brain GABAA receptor. Melatonin is an antioxidant. In bladder, treatment with melatonin prevents elevations in malondialdehyde levels, reverses changes in glutathione levels, and decreases myeloperoxidase levels compared with oxidative injury. It can normalize age induced bladder dysfunction through its antioxidant effects, inhibiting smooth muscle contractility directly and restoring impaired contractility via normalization of Ca2+ handling and sensitizations pathways. It attenuates the severity of cystitis and inflammation. Mast cell proliferation and activation are increased in cystitis, but decrease by melatonin treatment. Also, there is a decrease in expression levels of pro-inflammatory cytokines after melatonin treatment.

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