Enhancement of δ- but not μ-opiate agonist binding by calcium

  • Andreas Pfeiffer
  • Albert Herz


Present evidence for distinction of 2 types of opiate receptor sites in rat brain homogenates originates from different relative affinities of morphine-like alkaloids and enkephalins to δ-or enkephalin and μ- or morphine-receptor sites. We now report that Ca2+ in a physiological dose range (0.5–3 mM) enhances the binding of 3H-enkephalin in hypotonically treated rat brain membranes, whereas specific binding of 3H-morphine-like alkaloids is not affected. Furthermore, the potency of [d-Ala2, d-Leu5]-enkephalin to inhibit [3H]-diprenorphine and [3H]-ethylketazocine binding increased in the presence of Ca2+, whereas an increase in potency of [d-Ala2, d-Leu5]-enkephalin to inhibit binding of μ-receptor ligands was not observed. Kinetic analysis revealed that Ca2+ decreased the rate of dissociation of [d-Ala2, d-Leu5]-enkephalin without affecting the rate of association, thereby increasing the affinity. However, in saturation binding studies, performed in diencephalic membranes, in which [d-Ala2, d-Leu5]-enkephalin binds predominantly to μ-receptors, Ca2+ also increased the binding affinity of [3H]-[d-Ala2, d-Leu5]-enkephalin. Double reciprocal analysis suggested a mixed competitive-noncompetitive type of inhibition of [d-Ala2, d-Leu5]-enkephalin binding by dihydromorphine. Thus, the interactions of δ- and μ-opiate ligands with μ-receptors may involve topographically different, but closely related binding sites, located on a single receptor molecule.

Key words

Multiple opiate receptors Ca2+ 



[d-Ala2, d-Leu5]-enkephalin







FK 33-824

[d-Ala2, MePhe4, Met(O)-ol]-enkephalin


ethyleneglycol-bis-(β-aminoethylether) N, N'-tetraacetic acid


Tris (hydroxymethyl)-aminomethan


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Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Andreas Pfeiffer
    • 1
  • Albert Herz
    • 1
  1. 1.Department of NeuropharmacologyMax-Planck-Institut für PsychiatrieMünchen 40Germany

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