Octarphin, a nonopioid peptide of opioid origin
The data on the properties and the mechanism of action of the peptide octarphin (TPLVTLFK, fragment 12-19 of ß-endorphin), a selective agonist of the nonopioid (insensitive to the opioid antagonist naloxone) β-endorphin receptor detected on cells of the immune (peritoneal macrophages, T and β lymphocytes of the spleen and blood), endocrine (adrenal cortex, pituitary), and cardiovascular systems (cardiomyocytes) have been analyzed and systematized. When binding to the receptor, octarphin increases the mitogen- induced proliferation of T and B lymphocytes of human and mouse in vitro, activates murine peritoneal mac-rophages in vitro and in vivo, stimulates the growth of human T-lymphoblast cell lines Jurkat and MT-4, inhibits the activity of adenylate cyclase of rat adrenal cortex membranes, and suppresses the secretion of glucocorticoids from the adrenal gland to the blood. In the concentration range of 1-1000 nM, the peptide increases the activity of inducible NO synthase (iNOS) and the content of NO and cGMP in lipopolysaccharide-activated murine peritoneal macrophages. Taking into account that NO acts as a primary activator of soluble guanylate cyclase (sGC), it can be assumed that the activating effect of octarphin on macrophages is accomplished in the following way: an increase in iNOS expression → an increase in NO production → an increase in sGC activity → an increase in the intracellular cGMP level.