Hemorphin-4


Hemorphin-4 is an endogenous opioid peptide of the hemorphin family which possesses antinociceptive properties and is derived from the β-chain of hemoglobin in the bloodstream. It contains a tetrapeptide core with the amino acid sequence Tyr-Pro-Trp-Thr. Hemorphin-4 serves as a opioid receptor ligand that has affinities for the μ-, δ-, and κ-opioid receptors in the same range as the structurally related β-casomorphins, although affinity to the κ-opioid receptor is markedly higher in comparison. It acts as an agonist at these sites. It presents high affinity for other receptors such as angiotensin IV, bombesin subtype 3, and the corticotropin releasing factor. Even though it exhibits lower binding affinity for opioid receptors relative to traditional opioid peptides such as endorphins and enkephalins; it may still influence opioid receptor systems due to its high tissue concentration.

Therapeutic potentials

Hemorphin-4 also has inhibitory effects on angiotensin-converting enzyme, and as a result, may play a role in the regulation of blood pressure. Notably, inhibition of ACE also reduces enkephalin catabolism. Upon modifications with adamantane and cyclohexane, the Hemorphin-4 analog inhibits Insulin [regulated aminopeptidase|insulin-regulated aminopeptidase] compared to other angiotensin IV inhibitors, making it a suitable candidate for pain, anxiety, and depression therapies. In binding to the μ-opioid receptor, it has significant seizure-suppressing and pain-relieving properties and reduces involuntary bladder contractions in a similar manner to classic opioids.