Melatonin inhibits voltage-sensitive Ca(2+) channel-mediated neurotransmitter release.

Melatonin is involved in various neuronal functions such as circadian rhythmicity and thermoregulation. Melatonin has a wide range of pharmacologically effective concentration levels from the nanomolar to millimolar levels. Recently, the antiepileptic effect of high dose melatonin has been the focus of clinical studies; however, its detailed mechanism especially in relation to neurotransmitter release and synaptic transmission remains unclear. We studied the effect of melatonin at high concentrations on the neurotransmitter release by monitoring norepinephrine release in PC12 cells, and excitatory postsynaptic potential in rat hippocampal slices. Melatonin inhibits the 70mM K(+)-induced Ca(2+) increase at millimolar levels without effect on bradykinin-triggered Ca(2+) increase in PC12 cells. Melatonin (1mM) did not affect A2A adenosine receptor-evoked cAMP production, and classical melatonin receptor antagonists did not reverse the melatonin-induced inhibitory effect, suggesting G-protein coupled receptor independency. Melatonin inhibits the 70mM K(+)-induced norepinephrine release at a similar effective concentration range in PC12 cells. We confirmed that melatonin (100µM) inhibits excitatory synaptic transmission of the hippocampal Schaffer collateral pathway with the decrease in basal synaptic transmission and the increase in paired pulse ratio. These results show that melatonin inhibits neurotransmitter release through the blocking of voltage-sensitive Ca(2+) channels and suggest a possible mechanism for the antiepileptic effect of melatonin.

Moxibustion for managing type 2 diabetes mellitus: a systematic review.

OBJECTIVE: Moxibustion is currently used for treating diabetes mellitus (DM) as a non-drug intervention in East Asian countries. This systematic review aims to evaluate the effectiveness of moxibustion for managing the symptoms of type 2 DM patients. METHODS: We searched MEDLINE, AMED, EMBASE, CINAHL, The Cochrane Library, six Korean databases, and four Chinese databases. Risk of bias was used for evaluating the quality of the included studies. RESULTS: A total of 5 studies met the inclusion criteria for this review. All of the included studies had high risks of bias. One randomized clinical trial (RCT) compared the effectiveness of one-time moxibustion use with oral administration of glibenclimide and showed the significant effects of moxibustion on glycemic control. Another RCT tested the effectiveness of moxibustion plus conventional treatment, and the moxibustion group reported significant improvement in fasting and postprandial blood glucose levels compared with the conventional treatment group. Two RCTs compared the effectiveness of moxibustion versus acupuncture or moxibustion plus acupuncture, and the combined treatment showed the most favorable effects on the control of blood glucose, urine glucose, and glycocylated hemoglobin A(1c) (HbA(1c)). One uncontrolled observational study showed favorable effects of moxibustion on the response rate. CONCLUSIONS: It is difficult to conclude that moxibustion is an effective intervention for the control of type 2 DM due to the scarcity of trials and the low methodological quality of included studies. Further rigorous RCTs may be necessary to evaluate the effectiveness of moxibustion for type 2 DM.