MT₂Melatonin Receptors Are Present and Functional in Rat Caudal Artery

Abstract

In rat caudal artery, contraction to melatonin results primarily from activation of MT 1 melatonin receptors; however, the role of MT 2 melatonin receptors in vascular responses is controversial. We examined and compared the expression and function of MT 2 receptors with that of MT 1 receptors in male rat caudal artery. MT 1 and MT 2 melatonin receptor mRNA was amplified by reverse transcription-polymerase chain reaction from caudal arteries of three rat strains (i.e., Fisher, Sprague-Dawley, and Wistar). Antisense (but not sense) 33 P-labeled oligonucleotide probes specific for MT 1 or MT 2 receptor mRNA hybridized to smooth muscle, as well as intimal and adventitial layers, of caudal artery. In male Fisher rat caudal artery denuded of endothelium, melatonin was 10 times more potent than 6-chloromelatonin to potentiate contraction to phenylephrine, suggesting activation of smooth muscle MT 1 melatonin receptors. The MT 1 /MT 2 competitive melatonin receptor antagonist luzindole (3 M), blocked melatonin-mediated contraction (0.1-100 nM) with an affinity constant (K B value of 157 nM) similar to that for the human MT 1 receptor. However, at melatonin concentrations above 100 nM, luzindole potentiated the contractile response, suggesting blockade of MT 2 receptors mediating vasorelaxation and/or an inverse agonist effect at MT 1 constitutively active receptors. The involvement of MT 2 receptors in vasorelaxation is supported by the finding that the competitive antagonists 4-phenyl 2-acetamidotetraline and 4-phenyl-2-propionamidotetraline, at MT 2 -selective concentrations (10 nM), significantly enhanced contractile responses to all melatonin concentrations tested (0.1 nM-10 M). We conclude that MT 2 melatonin receptors expressed in vascular smooth muscle mediate vasodilation in contrast to vascular MT 1 receptors mediating vasoconstriction.Accumulating evidence indicates that the hormone melatonin regulates vascular tone; however, the nature of the response remains controversial. Both vasoconstrictor and vasodilator responses have been reported; however, data supporting the presence of melatonin receptors is found in some, but not all, vascular beds (Mahle et al., 1997). In isolated rat caudal arteries, nanomolar concentrations of melatonin potentiate contraction induced by either endogenous or exogenous vasoconstrictors (Viswanathan et al

The role of melatonin in diabetes: therapeutic implications

“…The hormone exerts its effects both through activation of its receptors (21), through the circulating levels of the hormone or in a more autocrine/paracrine fashion near target tissues (22,23). In addition, melatonin brings about vasoconstriction through the MT1 and vasodilation through the MT2 receptors (24). It lowers cortisol secretion (25) in the adrenal cortex, similar to the action shared with insulin (23).…”

Melatonin inhibits nitric oxide production by microvascular endothelial cells in vivo and in vitro

“…More recently, functional assays in vitro suggested that melatonin is involved in the control of vasomotor tone and acts via receptors located in the myocytes (Masana et al, 2002) and/or in the endothelium (Geary et al, 1998;Yang et al, 2001). In another experimental model, melatonin was shown to inhibit the rolling of leukocytes on the venular endothelial layer in vivo by stimulating MT 2 melatonin receptors (Lotufo et al, 2001).…”

Effect of L-NAME-induced hypertension on melatonin receptors and melatonin levels in the pineal gland and the peripheral organs of rats

“…10 Expression of MT 1 and MT 2 receptor mRNA was found in different parts of the cardiovascular system, such as the heart, 11 coronary artery, aorta 12 and cerebral 13 and caudal arteries. 14 In the cardiovascular system, MT 1 and MT 2 receptor proteins were found in the heart 11 and coronary artery. 15 Activation of the MT 1 receptor causes vasoconstriction in the rat caudal artery, which is believed to be involved in the thermoregulation, 16 and activation of MT 2 results in vasodilatation.…”