For Research Use Only – Not for Human Consumption

Abstract

The melatonin receptor type 2 (MT2) is a G protein–coupled receptor (GPCR) that plays an essential role in regulating circadian rhythms, phase-shifting responses to light, and vascular tone. Alongside MT1, MT2 mediates the biological effects of melatonin, particularly those linked to photic entrainment of the circadian clock. Research on MT2 has expanded due to its potential implications in sleep regulation, mood disorders, and cardiovascular physiology.

Introduction

Melatonin, a neurohormone secreted by the pineal gland, acts on two primary receptor subtypes: MT1 (MTNR1A) and MT2 (MTNR1B). While MT1 is primarily associated with circadian rhythm stabilization and inhibition of neuronal activity, MT2 receptors are more strongly associated with phase-shifting of circadian rhythms and modulation of vascular function.

MT2 research has gained interest for its role in chronotherapy, psychiatric disorders, and glucose regulation. Unlike MT1, which predominates in the suprachiasmatic nucleus (SCN), MT2 shows a broader distribution in the SCN, retina, and vascular tissues.

Chemical Identification

• Primary Ligand: Melatonin
• Melatonin CAS Number: 73-31-4
• MT2 Gene Name: MTNR1B
• Protein Classification: G protein-coupled receptor (GPCR)

Mechanism of Action in Research

MT2 receptors are primarily coupled to inhibitory G proteins (Gi/o), reducing cyclic AMP (cAMP) and, in some systems, activating phosphoinositide signaling pathways.

Key MT2 functions under study:

• Circadian Phase-Shifting – MT2 helps reset the circadian clock in response to light and melatonin signals.
• Retinal Physiology – MT2 mediates melatonin’s effects on retinal photoreceptor activity.
• Vascular Tone – MT2 has been implicated in melatonin’s effects on vasodilation and cardiovascular regulation.
• Metabolic Regulation – MT2 polymorphisms (MTNR1B) have been linked to altered glucose metabolism and type 2 diabetes risk.

Applications in Scientific Research

1. Circadian Biology – Investigating melatonin’s role in sleep/wake phase shifts.
2. Sleep Disorders – Examining MT2 modulation in insomnia and jet lag models.
3. Ophthalmology – Studying retinal photoreceptor adaptation and signaling.
4. Cardiovascular Studies – Exploring MT2’s effects on vascular tone and blood pressure regulation.
5. Metabolic Research – Assessing associations between MT2 and glucose homeostasis.

Safety & Compliance

Research compounds acting on MT2 are not FDA-approved for medical treatment, dietary use, or supplementation. They are supplied strictly for laboratory research only.

References (PubMed/NCBI Examples)

1. Dubocovich ML, et al. “International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors.” Pharmacol Rev. 2010. [PubMed PMID: 20123979]
2. Liu C, Weaver DR, Jin X, et al. “Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock.” Neuron. 1997. [PubMed PMID: 9208850]
3. Lyssenko V, et al. “Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion.” Nat Genet. 2009. [PubMed PMID: 19060908]

Disclaimer

This information is provided for laboratory research purposes only. Compounds targeting MT2 receptors are not for human consumption, veterinary use, diagnostic, or therapeutic application. Handling must follow institutional biosafety guidelines.

Frequently Asked Questions (FAQ)

1. What is MT2?
MT2 is a melatonin receptor subtype involved in circadian phase-shifting, retinal signaling, and vascular regulation.

2. What is the CAS number for melatonin, its main ligand?
The CAS number is 73-31-4.

3. How does MT2 differ from MT1 receptors?
MT2 primarily mediates phase-shifting and vascular effects, while MT1 focuses on circadian stabilization and neuronal inhibition.

4. Where are MT2 receptors expressed?
They are expressed in the SCN, retina, pituitary, and vascular tissues.

5. What signaling pathway does MT2 use?
MT2 receptors act through Gi/o proteins to reduce cAMP and sometimes activate phosphoinositide signaling.

6. What research applications involve MT2?
Circadian rhythm studies, sleep regulation, cardiovascular physiology, and glucose metabolism research.

7. Is MT2 associated with any diseases?
Yes, MT2 polymorphisms (MTNR1B) have been linked to type 2 diabetes and altered glucose regulation.

8. Are MT2-targeting compounds FDA-approved?
No. They are for research only, not for clinical or dietary use.

9. Can MT2 modulation affect sleep patterns?
Yes, MT2 plays a key role in adjusting sleep/wake phases and circadian adaptation.

10. Where can MT2 studies be accessed?
Peer-reviewed journals and PubMed host extensive research on MT2 receptor biology.