Opiorphin 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 ...

chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...

first isolated from

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...

. Initial research with

mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

shows the compound has a painkilling effect greater than that of

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

. It works by stopping the normal breakup of

enkephalin An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephali ...

s, natural pain-killing

opioids Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

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 ...

. It is a relatively simple molecule consisting of a five-

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

, Gln-

Arg Arg or ARG may refer to: Places *''Arg'' () means "citadel" in Persian, and may refer to: **Arg, Iran, a village in Fars Province, Iran **Arg (Kabul), presidential palace in Kabul, Afghanistan **Arg, South Khorasan, a village in South Khorasan P ...

- Phe-

Ser Ser or SER may refer to: Places * Ser, a village in Bogdand Commune, Satu Mare County, Romania * Serpens (Ser), an astronomical constellation of the northern hemisphere * Serres, known as Ser in Serbian, a city in Macedonia, Greece Organization ...

-Arg (QRFSR). Opiorphin pentapeptide originates from the

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

region of the protein PROL1 (proline-rich, lacrimal 1). Opiorphin inhibits three

proteases A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...

: neutral ecto-endopeptidase ( MME), ecto-aminopeptidase N ( ANPEP) and perhaps also a dipeptidyl peptidase

DPP3 Dipeptidyl-peptidase 3 is an enzyme that in humans is encoded by the ''DPP3'' gene. This gene encodes a protein that is a member of the S9B family in clan SC of the serine proteases. This cytoplasmic protein binds a single zinc ion with its zinc-b ...

. Such action extends the duration of enkephalin effect where the natural pain killers are released physiologically in response to specific potentially painful stimuli, in contrast with administration of narcotics, which floods the entire body and causes many undesirable adverse reactions, including addiction liability and constipation. In addition, opiorphin may exert anti-depressive and antipanic action. Therapeutic application of opiorphin in humans would require modifying the molecule to avoid its rapid degradation in the intestine and its poor penetration of the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...

. This modification is done in the body by transformation of N-terminal glutamine into pyroglutamate. This form preserves the analgesic properties of opiorphin but with increased pharmaceutical stability.

References

{{Opioidergics Analgesics Neuropeptides Enkephalinase inhibitors Opioid peptides Peripherally selective drugs

See also

References