Selective conversion of β-endorphin into peptides related to γ- and α-endorphin

Abstract

β-Endorphin (β-LPH_61–91) is a well known endogenous opioid ligand. It and related peptides have recently been implicated in the control of adaptive behaviour. Smaller β-endorphin fragments appeared to be more active moieties than the parent molecule in a number of behavioural situations¹. Their effects seemed to occur independently of interaction with opiate receptor sites in the brain. Moreover, elimination of the opiate-like properties of γ-endorphin (β-LPH_61–77) by removing the N-terminal amino acid yielded des-tyrosine-γ-endorphin (β-LPH_62–77, dTγE) which had greater behavioural activity than γ-endorphin^2,3. The CNS effects of dTγE resembled those of neuroleptic drugs in several test systems, α-Endorphin (β-LPH_61–76) exerted effects opposite to those of dTγE and in some aspects its activity was comparable to that of psychostimulant drugs⁴. This opposition of effects suggests that a balance between γ- and α-type endorphins is involved in the control of brain function⁵. We report here that either γ-endorphin and dTγE or α-endorphin and des-tyrosine-α-endorphin (β-LPH_62–769 dTαE) can be formed preferentially from β-endorphin by enzymes associated with an enriched synaptosomal plasma membrane fraction from brain. It is suggested that these enzymes have a role in brain homeostatic mechanisms by regulating the generation of these substances.