OPRM1

OPRM1 Full Name

opioid receptor, mu 1

OPRM1 Introduction

M μ - opioid receptors are a type of opioid receptor with high affinity for enkephalin and β - endorphin, but low affinity for enkephalin. It is an inhibitory G protein coupled receptor that can activate the Gi α subunit, inhibit adenylate cyclase activity, and reduce cAMP levels. Mu opioid receptor 1 (MOR-1) is the main molecular target responsible for the deep analgesic and euphoric effects of endogenous opioid peptides and exogenous opioid drugs, including morphine, heroin, fentanyl, and hydrocodone. As a member of the A-class G protein coupled receptor (GPCR) family, it is encoded by the OPRM1 gene. MOR is widely distributed in the central and peripheral nervous systems, and is the main mediator of the benefits and major adverse reactions of opioid therapy, such as respiratory depression, constipation, physical dependence, and addiction. The study of the complex biology of MOR aims to distinguish its beneficial analgesic signals from pathways leading to harmful side effects, which is considered crucial for the development of safer pain therapies.

Figure. Active and inactive μ-opioid receptors.(Source: Zhorov BS, et al, 2000)

Structure
The structure of OPRM1 has been determined by antagonists β - DNA and alvimopan. Many structures in the active state are also available, including agonists such as DAMGO, beta endorphins, fentanyl, and morphine. The structure with the agonist BU72 has the highest resolution, but contains unexplainable features that may be experimental artifacts. This abundant evidence enables structure based design to create a novel class of opioid drugs with functional selectivity. The human MOR is encoded by the OPRM1 gene located on chromosome 6q25.2. This gene has undergone extensive alternative splicing, resulting in a large number of splicing variants (such as MOR-1A, MOR-1B, MOR-1K), which have different C-terminal tails and, in some cases, different intracellular loops. These variants can exhibit different tissue expression patterns, cellular transport behavior, and signaling characteristics. This molecular diversity is believed to contribute to the broad physiological and pharmacological effects triggered by MOR activation, indicating that specific variants may be targets for more selective therapeutic outcomes.

Physiological Effects and Functions
OPRM1 is the core of steady-state regulation and adaptive behavior:
Analgesia (pain suppression): Its most critical function is to inhibit the spread of nociceptive (pain) at multiple levels of the neural axis, providing strong relief for acute and chronic pain.
Reward and reinforcement: Activation of OPRM1 on GABAergic interneurons in VTA inhibits dopaminergic neurons, leading to the release of dopamine in NAc. This mechanism is crucial for enhancing pleasurable experiences, natural rewards, and addictive drug properties.
Stress and emotional response: The OPRM1 signal regulates the body's response to stress, helping to regulate emotions, and its connection with anti anxiety and anti depression effects depends on brain circuits.

Alternate Names for OPRM1

OPRM1; opioid receptor, mu 1; mor; Oprm; muOR; MOP-R; MOR-1; M-OR-1; MOR-1O; mu-type opioid receptor; MOP receptor; mu opioid receptor splice variant mMOR-1Z;

• 1.Zhorov BS, Ananthanarayanan VS. Homology models of μ-opioid receptor with organic and inorganic cations at conserved aspartates in the second and third transmembrane domains. Archives of Biochemistry and Biophysics. 2000,375(1):31-49.