Enkephaline

Enkephaline, more commonly called enkephalin, is an endogenous opioid peptide that functions as a neurally derived modulator of pain and emotion. The two principal forms are Met-enkephalin (Tyr-Gly-Gly-Phe-Met) and Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu), both pentapeptides derived from the larger precursor protein proenkephalin A. They are produced and released by neurons in the central nervous system and certain peripheral tissues.

Enkephalins act as endogenous ligands for opioid receptors, with a preference for delta opioid receptors and additional activity at mu receptors, while showing limited interaction with kappa receptors. Upon receptor binding, they inhibit adenylyl cyclase activity, modulate ion channel conductance, and decrease the release of excitatory neurotransmitters in pain pathways, thereby contributing to analgesia and modulation of nociceptive signaling. They also influence mood, stress responses, and gut motility through similar receptor-mediated mechanisms.

Biosynthesis and distribution are tightly regulated, with enkephalins stored in vesicles and released in response to neural activity. After exerting their effects, they are rapidly degraded by enkephalinases, including aminopeptidase N and neutral endopeptidase (neprilysin), leading to a short physiological half-life. This rapid breakdown limits their duration of action and has implications for therapeutic exploitation.

In physiology and pharmacology, enkephalins are considered among the body’s natural analgesic systems. Their properties have informed research into analgesic strategies, including the development of stable analogs and enzyme inhibitors, aimed at enhancing endogenous pain control while minimizing side effects.