Isolation of a novel endogenous opiate analgesic from human blood.

Based upon its ability to inhibit opiate receptor binding, a low-molecular-weight substance (600) has been isolated from human plasma by extraction into butanol and ion exchange, molecular sieve, and thin-layer chromatography. When this substance, termed anodynin, is microinjected into rat periaqueductal gray matter, it causes a profound, long-lasting analgesia which is prevented by prior injection of the opiate antagonist naloxone. Anodynin (opiate receptor binding material) levels in serum from hypophysectomized rats are less than 5% of values obtained in sham-operated controls. Anodynin differs from enkephalin, a morphine-like peptide isolated from brain, in its sensitivity to enzymatic loss of opiate receptor inhibitory potency, thin-layer chromatographic mobility, and behavioral effects. Anodynin might be a hormone that acts on peripheral opiate receptors in the classical manner, but might also, due to its lipophilic nature and small size, penetrate into the brain to produce centrally mediated behavioral effects.