MT1 and MT2 melatonin receptors are expressed in nonoverlapping neuronal populations

Abstract

Melatonin (MLT) exerts its physiological effects principally through two high‐affinity membrane receptors MT1 and MT2. Understanding the exact mechanism of MLT action necessitates the use of highly selective agonists/antagonists to stimulate/inhibit a given MLT receptor. The respective distribution of MT1 and MT2 within the CNS and elsewhere is controversial, and here we used a “knock‐in” strategy replacing MT1 or MT2 coding sequences with a LacZ reporter. The data show striking differences in the distribution of MT1 and MT2 receptors in the mouse brain: whereas the MT1 subtype was expressed in very few structures (notably including the suprachiasmatic nucleus and pars tuberalis), MT2 subtype receptors were identified within numerous brain regions including the olfactory bulb, forebrain, hippocampus, amygdala and superior colliculus. Co‐expression of the two subtypes was observed in very few structures, and even within these areas they were rarely present in the same individual cell. In conclusion, the expression and distribution of MT2 receptors are much more widespread than previously thought, and there is virtually no correspondence between MT1 and MT2 cellular expression. The precise phenotyping of cells/neurons containing MT1 or MT2 receptor subtypes opens new perspectives for the characterization of links between MLT brain targets, MLT actions and specific MLT receptor subtypes.

SIRT1 Mediates Melatonin’s Effects on Microglial Activation in Hypoxia: In Vitro and In Vivo Evidence

“…Melatonin selectively activates two G-protein coupled receptors, MT1 (or MTNR1a) and MT2 (or MTNR1b), which differ in tissue distribution, molecular structure, and downstream pathways [12][13][14][15]. The MT1 isoform, in particular, has been linked to neuroprotective actions of melatonin in different models [16][17][18] and appears to be the prevalent site of action of melatonin in human fetal brains [17].…”

<p>Role of Melatonin in the Regulation of Pain</p>

“…When they do, one of them dominates the cell membrane. 56 MT1 may play an important role in the signaling pathway transduction of the nervous system. Recent research indicates that MT1 receptor is involved in neural pathways modulating depression and diurnal rhythms.…”

Melatonin enhances thrombopoiesis through ERK1/2 and Akt activation orchestrated by dual adaptor for phosphotyrosine and 3‐phosphoinositides

“…Melatonin (MT), primarily synthesized in the pineal gland and entrained by photic environment, conveys endocrine signals to multiple sites containing MT receptors . Most of its well‐documented actions are mediated through two G‐protein‐coupled membrane receptors, MT1 and MT2 . Hematopoietic progenitor activities are influenced by MT, as evidenced by its capacity to rescue the natural colony‐forming ability of pinealectomized mice .…”

“…10 Most of its well-documented actions are mediated through two G-protein-coupled membrane receptors, MT1 and MT2. 11,12 Hematopoietic progenitor activities are influenced by MT, as evidenced by its capacity to rescue the natural colony-forming ability of pinealectomized mice. 13 The peripheral platelet number in patients with thrombopenia also rapidly increases in response to MT, suggesting that MT influences MK activities.…”