The presence of melatonin receptors and inhibitory effect of melatonin on hydrogen peroxide‐induced endothelial nitric oxide synthase expression in bovine cerebral blood vessels

Abstract

Melatonin plays a key role in a variety of important physiological functions including influencing cerebral blood vessels. Therefore, in the present study, we have identified the existence of melatonin receptors and test the effect of melatonin on hydrogen peroxide-induced endothelial nitric oxide synthase (eNOS) expression in bovine cerebral arteries. The results indicate that mt1A melatonin receptor mRNA is expressed in bovine cerebral arteries. The relative levels of mt1A melatonin receptor mRNA expression in anterior, posterior, middle and vertebral cerebral arteries were compared. The data show the highest and lowest levels of mRNA expressions in the middle and vertebral cerebral arteries, respectively. The maximal number (B(max)) of different types of melatonin receptors in various regions of cerebral arteries were identified and further characterized by using the selective 2-[(125)I] iodomelatonin binding assay. Saturation studies revealed that the binding represented a single site of high affinity binding for the melatonin receptor with the highest and lowest binding capacities in the middle and vertebral arteries, respectively. In order to elaborate the functional significance of melatonin in cerebral blood vessels, hydrogen peroxide- induced induction in eNOS protein level and phosphorylation of calcium/calmodulain-dependent protein kinase II (phospho-CaMKII) were demonstrated in the bovine isolated cerebral arteries with these effect being abolished by melatonin. This is the first evidence showing expression of mt1A melatonin receptor in the bovine cerebral arteries. However, further studies are necessary to delineate the role of melatonin and its receptors in regulating physiology of the cerebral vessels.

Basal brain oxidative and nitrative stress levels are finely regulated by the interplay between superoxide dismutase 2 and p53

“…C). The increase of mitochondrial PC in SOD2 −/+ mice is consistent with the proposed antioxidant role of SOD2 (Williams et al, ; Miao and St. Clair, ), whereas the increase of mitochondrial 3‐NT levels in TgSOD2 mice could result from the well‐known ability of SOD2‐derived H 2 O 2 to induce NOS and thus NO production (Shimizu et al, ; Ha et al, ; Chucharoen et al, ). Although the observation that no changes with regard to PC or protein‐bound HNE levels were found in the whole‐brain homogenate obtained from both SOD2 −/+ and TgSOD2 mice is in agreement with a previous work (Ibrahim et al, ), it remains to be understood why a reduction of 3‐NT levels has been observed.…”

Melatonin improves cerebrovascular function and decreases oxidative stress in chronically hypoxic lambs

“… showed direct, MT1R‐ and MT2R‐independent vasodilator effects of melatonin in fetal cerebral arteries, which might be related with a local sympathetic‐inhibitory mechanism, able to diminish norepinephrine‐induced contraction. In this sense, at least MT1R is highly expressed in bovine MCA . Although we did not quantify expression or activity of MT receptors, in our model, melatonin might be acting by both MTR‐dependent and independent pathways.…”

Melatonin promotes triacylglycerol accumulation via MT2 receptor during differentiation in bovine intramuscular preadipocytes

“…In mammals, numerous physiological roles of melatonin are mediated via activation of two high-affinity G protein-coupled receptors, MT1 and MT2 28 , 29 , which are expressed both singly and together in various tissues with different expression profiles 30 – 32 . Regarding the mediation of melatonin functions, MT1 and MT2 receptors appear to vary among different tissues and cell types, and even within the same cell type 29 , 33 .…”