Selective conversion of beta-endorphin into peptides related to gamma- and alpha-endorphin
Burbach, J.P.; Loeber, J.G.; Verhoef, J.; Wiegant, V.M.; de Kloet, E.R.; de Wied, D.
Nature 283(5742): 96-97
1980
ISSN/ISBN: 0028-0836 PMID: 7350533 Document Number: 158891
beta-Endorphin (beta-LPH61-91) is a well known endogenous opioid ligand. It and related peptides have recently been implicated in the control of adaptive behaviour. Smaller beta-endorphin fragments appeared to be more active moieties than the parent molecule in a number of behavioural situations. Their effects seemed to occur independently of interaction with opiate receptor sites in the brain. Moreover, elimination of the opiate-like properties of gamma-endorphin (beta-LPH61-77) by removing the N-terminal amino acid yielded des-tyrosine-gamma-endorphin (beta-LPH62-77, dT gamma E) which had greater behavioural activity than gamma-endorphin. The CNS effects of dT gamma E resembled those of neuroleptic drugs in several test systems. alpha-Endorphin (beta-LPH61-76) exerted effects opposite to those of dT gamma E and in some aspects its activity was comparable to that of psychostimulant drugs. This opposition of effects suggests that a balance between gamma- and alpha-type endorphins is involved in the control of brain function. We report here that either gamma-endorphin and dT gamma E or alpha-endorphin and des-tyrosine-alpha-endorphin (beta-LPH62-76, DT alpha E) can be formed preferentially from beta-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.