Endomorphin-2 (EM-2) is an

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

opioid peptide Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but th ...

and one of the two

endomorphin Endomorphins are considered to be natural opioid neurotransmitters central to pain relief. The two known endomorphins, endomorphin-1 and endomorphin-2, are tetrapeptides, consisting of Tyr-Pro-Trp-Phe and Tyr-Pro-Phe-Phe amino acid sequences resp ...

s. It has the

amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthes ...

Tyr-Pro-Phe-Phe-NH₂. It is a high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Partn ...

, highly selective

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical � ...

, and along with endomorphin-1 (EM-1), has been proposed to be the actual endogenous

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...

of this receptor (that is, rather than the

endorphin Endorphins (contracted from endogenous morphine) are chemical signals in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in an area of the brain known as the pituitary gland. Hist ...

s). Like EM-1, EM-2 produces

analgesia Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...

in animals, but whereas EM-1 is more prevalent in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

, EM-2 is more prevalent in the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...

. In addition, the action of EM-2 differs from that of EM-1 somewhat, because EM-2 additionally induces the release of

dynorphin A Dynorphin A is a dynorphin, an endogenous opioid peptide with the amino acid sequence: Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys. Dynorphin A1–8 is a truncated form of dynorphin A with the amino acid sequence: Tyr-Gly-Gly-Phe-Leu-Ar ...

and et/nowiki>enkephalin in the spinal cord and brain by an unknown

mechanism Mechanism may refer to: *Mechanism (engineering), rigid bodies connected by joints in order to accomplish a desired force and/or motion transmission *Mechanism (biology), explaining how a feature is created *Mechanism (philosophy), a theory that a ...

, which in turn go on to activate the κ- and

δ-opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous lig ...

s, respectively, and a portion of the analgesic effects of EM-2 is dependent on this action. Moreover, while EM-1 produces

conditioned place preference Conditioned place preference (CPP) is a form of Pavlovian conditioning used to measure the motivational effects of objects or experiences. This motivation comes from the pleasurable aspect of the experience, so that the brain can be reminded of th ...

, a measure of

drug reward Brain stimulation reward (BSR) is a pleasurable phenomenon elicited via direct stimulation of specific brain regions, originally discovered by James Olds and Peter Milner. BSR can serve as a robust operant reinforcer. Targeted stimulation activate ...

, EM-2 produces conditioned place ''aversion'', an effect which is dynorphin A-dependent. Similarly to the case of EM-1, the

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

encoding for EM-2 has not yet been identified.

References

{{Opioidergics Mu-opioid receptor agonists Neuropeptides

See also

References