ABSTRACT
Melatonin (5-methoxy-N-acetyltryptamine) is a neurohormone synthesized in the pineal gland, which is located on the midline, attached to the posterior end of the roof of the third ventricle in the brain, mainly during the night, and it affects a number of heart functions such as cardiac rhythms, arterial blood pressure, and heart rate [1,2]. Light has an inhibitory effect on pineal melatonin secretion [1]. Melatonin release is synchronized with daylight cycle by a multisynaptic pathway. Sympathetic nerve stimulation from the intermediolateral nucleus occurs after interpolation in the superior cervical ganglion is £nally directed to the epiphysis to induce melatonin synthesis [3]. The activity of rate-limiting enzymes in the epiphysis is regulated by norepinephrine binding to pineal β1 and α1 adrenoceptors [4,5]. The local renin-angiotensin system may also effect melatonin secretion [6]. Nonspeci£c mechanisms of melatonin action can also reside in direct interaction with calmodulin, a small, acidic protein approximately 148 amino acids long (16,706 Da), inhibition of calcium (Ca2+) channels, or calcium pump stimulation observed in cardiomyocytes [7-9]. The interference of melatonin synthesis and action with other neurohumoral systems plays a crucial role in the regulation of cardiovascular functions by melatonin. The physiological actions of melatonin depend on membrane receptors in melatonin-responsive cells and tissues [10]. Melatonin mainly has two membrane receptors called MT1 and MT2, which are G protein-coupled receptors, and has intracellular signaling proteins such as quinon reductase 2, calmodulin, calreticulin, and tubulin. The third receptor type, MT3, which has a lower af£nity, is probably not coupled with G protein [11]. In the cardiovascular system, whereas the MT1 receptor was found in chicken and human coronary arteries as well as in rat heart [12,13], the MT2 receptor was identi£ed in the human heart, coronary arteries, and the aorta [14]. When melatonin receptors are activated, some interactions start in the cell including alterations in the levels of cyclic nucleotides (cAMP, cGMP) and calcium, activation of protein kinase C subtypes, intracellular localization of steroid hormone receptors, and regulation of G protein signaling proteins.
