Disease relevance of Mtnr1a

• Melatonin-induced phase shifts, however, are only modestly altered in the receptor-deficient mice; pertussis toxin still blocks melatonin-induced phase shifts in Mel1a receptor-deficient mice [1].
• CONCLUSION: Point mutations of hAR are not necessary for metastatic prostate cancer, while alterations in the solyglutamine and polyglycine repeat region in exon 1 of the MR gene are more often found [2].
• CONCLUSION: Chronic hyperglycemia may add to the age-related decrease in M-receptor-mediated insulin release by affecting the buffering capacity of the islets through mechanisms other than amiloride-sensitive proton exchange [3].

High impact information on Mtnr1a

• Three distinct phenotypes were studied: 1) the common phenotype (slg+, HLA-DR+, MR+, T65+, Lyt-3-); 2) the T-cell phenotype (slg-, HLA-DR-, MR-, T65+, Lyt-3+); and 3) a unique phenotype (slg-, HLA-DR+, MR+, T65+, Lyt-3-) [4].
• Both immunoglobulin M receptor-induced Ca(2+) flux and proliferation in response to B-cell mitogens are attenuated [5].
• In contrast, the energy depleter 2,4-dinitrophenol, which inhibits normal insulin receptor retroendocytosis, impaired M receptor recycling 4-fold more effectively than that of WT [6].
• The T1-M receptor is abundantly expressed in single cells of the major hemopoietic organs (embryonic liver, spleen, bone marrow) [7].
• The Mel1a melatonin receptor is coupled to parallel signal transduction pathways [8].

Biological context of Mtnr1a

• 1. An interspecific backcross analysis revealed that the mouse gene (Mtnr1a) maps to the proximal portion of chromosome 8 [9].
• These results provide information on Mel1a receptor gene structure essential for designing transgenic and gene knock-out studies and analyzing the transcriptional regulation of receptor gene expression [10].
• In both the common and unique phenotypes, TPA increased the expression of T65 and HLA-DR, decreased the formation of MR, and induced cytoplasmic immunoglobulin, but it did not induce Lyt-3 [4].
• Revertants (MelR) isolated during the course of the cumulative mortality experiment were used to compare virulence in isogenic sets of Mel- and MelR [11].
• To identify brain structures potentially acting as biological clocks in rainbow trout (Oncorhynchus mykiss), the expression sites of a trout homolog of the mouse clock gene were studied and compared with that of melatonin receptors (Mel-R) [12].

Anatomical context of Mtnr1a

• The 5'-flanking region drives luciferase expression 114-fold over basal levels in a murine retinal cell line that endogenously expresses the Mel1a receptor [10].
• According to the developmental stages, gene for MelR was differently expressed on ovary, hypothalamus, and pituitary [13].
• In the ovary, the expression signal of MelR gene was identified on granulosa cells [13].
• 1. Mouse fibroblasts (NIH3T3) transfected with the full-length coding region of the Mel1a melatonin receptor stably expressed the receptor, coupled to a pertussis toxin-sensitive G-protein(s) and exhibiting high affinity and adequate pharmacological profile [14].
• In addition, in situ hybridization with a glutamate decarboxylase 65 probe, demonstrates that cells expressing clock and Mel-R in the optic tectum are gamma-aminobutyric acid neurons [12].

Associations of Mtnr1a with chemical compounds

• The Mel1a receptor accounts for all detectable, high affinity melatonin binding in mouse brain [1].
• 1. Concentration-effect curves were obtained, in the absence and presence of histamine H2-receptor blockade, to 5-methylfurmethide (5-MeF) and McN-A 343, high efficacy and low efficacy acetylcholine (ACh) M-receptor agonists, respectively, in isolated stomach preparations from the mouse and immature rat and guinea-pig [15].
• In conclusion, our study suggests that the mechanisms of PCH action against soman-induced seizures might differ from those of the M receptor antagonists atropine and scopolamine, and that of the antagonist of both the M and N receptors, 8018 [16].
• Dopamine induced phospho-CREB-ir exclusively in GABA-ir neurons and melatonin reversed this effect of dopamine, indicative of an inhibitory Gi protein linking via the Mel1a receptor to adenylyl cyclase [17].
• The oral administration of YZF to the senile mice increased the M-R concentration, while the concentration of Ach and the activity of MAO-B decreased in senile mice brains [18].

Other interactions of Mtnr1a

• Of two sub-types cloned from mammals (Mel1a and Mel1b), the Mel1a receptor appears to mediate the circadian and reproductive effects of the hormone [10].
• Thus, melatonin modulates PACAP-mediated retinal stimuli for clock entrainment primarily via the Mel1a melatonin receptor through molecular interaction within the cAMP-signalling pathway [19].

Analytical, diagnostic and therapeutic context of Mtnr1a

• In situ hybridization studies establish that Mel1a receptor messenger RNA is expressed in the hypothalamic suprachiasmatic nuclei and hypophyseal pars tuberalis, presumed sites of the circadian and some of reproductive actions of melatonin, respectively [10].
• We first subcloned by PCR a partial cDNA encoding the Mel1a receptor from Syrian hamster SCN [20].

References