Enkephalinlike

Enkephalin-like describes peptides that resemble enkephalins in sequence or function. The term is most often used for the endogenous pentapeptides met-enkephalin and leu-enkephalin, which are derived from the larger precursor protein proenkephalin A. Met-enkephalin and leu-enkephalin have the sequences Tyr-Gly-Gly-Phe-Met and Tyr-Gly-Gly-Phe-Leu, respectively, and both act at opioid receptors to modulate pain signaling.

Biology and receptors: Enkephalins primarily bind to delta opioid receptors, with additional activity at mu receptors. This receptor engagement leads to analgesic effects in the central nervous system, and to a lesser extent in peripheral tissues. The activity of enkephalins contributes to natural pain relief, stress responses, and modulation of mood and reward circuits.

Synthesis and degradation: Enkephalins are produced through proteolytic processing of proenkephalin A. They are rapidly inactivated by peptidases, including enkephalinases such as aminopeptidases and other peptidases, giving them a short duration of action. This rapid turnover has spurred the development of enkephalin analogs designed to resist degradation and to improve receptor selectivity.

Distribution and relevance: Enkephalin-like peptides are widely distributed in brain regions involved in pain processing, autonomic control, and emotion, as well as in the spinal cord and some peripheral tissues. They participate in physiological analgesia and are a focus of research into analgesic drug design, including strategies to enhance stability and target specific opioid receptor subtypes.