Expression of Melatonin Receptors in Arteries Involved in Thermoregulation

Melatonin binding sites were localized and characterized in the vasculature of the rat by using the melatonin analogue 2-[125I]iodomelatonin (125I-melatonin) and quantitative in vitro autoradiography. The expression of these sites were restricted to the caudal artery and to the arteries that from the circle of Willis at the base of the brain. The arterial125I-melatonin binding was stable, saturable, and reversible. Saturation studies revealed that the binding represented a single class of high-affinity binding sites with a dissociation constant (Kd) of 3.4 x 10-11M in the anterior cerebral artery and 1.05 x 10-10M in the caudal artery. The binding capacities (Bmax) in these arteries were 19 and 15 fmol/mg of protein, respectively. The relative order of potency of indoles for inhibition of125I-melatonin binding at these sites was typical of a melatonin receptor: 2-iodomelatonin > melatonin > N-acetylserotonin >>> 5-hydroxytryptamine. Norepinephrine-induced contraction of the caudal artery in vitro was significantly prolonged and potentiated by melatonin in a concentration-dependent manner, suggesting that these arterial binding sites are functional melatonin receptors. Neither primary steps is smooth muscle contraction (inositol phospholipid hydrolysis) nor relaxation (adenylate cyclase activation) were affected by melatonin. Melatonin, through its action on the tone of these arteries, many cause circulatory adjustments in these arteries, which are believed to be involved in thermoregulation.