Download mechanisms for activation and inactivation of endorphins

M O N D A Y 30 MARCH
SYMPOSIUM 7
Mon-S7-1
ReCEPTORS FOR ENKEPHALINS AND ENDORPHINS
H.W. Kosterlitz, S.J.
Paterson and L.E. Robson
Unit for Research on Addictive Drugs, University of Aberdeen, Aberdeen AB9 lAS,
U.K.
The concept that the population of receptor sites for the enkephalins and
endorphins is heterogeneous, is based on the following experimental approaches.
When the peptides are assayed in two pharmacological and two binding models,
the rank order of activity differs in the four systems.
The antagonist effect
of naloxone is smaller on the &receptors in the mouse vas deferens than on its
Cold ligands of the p-type protects the binding of tritiated
p-receptors.
The selective pp-agonists better than that of 6-agonists, and vice versa.
agonist , D-Ala2-MePhe4-Gly-ol’-enkephalin and the selective 6-agonist, D-Ala2D-Leu’-enkephalin each occupy significantly less than half of the total number
These observations
of sites available in homogenates of guinea-pig brain.
Certain benzoindicate the presence of a third receptor, the K-binding site.
morphans, e.g. ethylketazocine, bind as K-agOniStS to this site from which they
are displaced only by very high concentrations of p- or 6-agonists.
Since,
the available K-agOniStS cross react with the p-binding site and to a lesser
extent with the &-binding site, the capacity of the K-binding sites is determined with tritiated ethylketazocine in the presence of unlabelled p- and 6The approximate percentages of p-, 6- and K-binding sites in
agonists.
(Supported
homogenate of guinea-pig brain are 25, 45 and 30%, respectively.
by grants from the Medical Research Council and the U . S . National Institute on
Drug Abuse, DA 00662).
Mon-S7-2
MECHANISMS FOR ACTIVATION AND INACTIVATION OF ENDORPHINS
D.G.
Smyth, Laboratory o f Peptide Chemistry, National Institute f o r
Medical Research, The Ridgeway, Mill Hill, London “7 IAA.
22P