DISCRIMINATION OF 3 TYPES OF OPIOID BINDING-SITES IN RAT-BRAIN INVIVO

  • 1 January 1984
    • journal article
    • research article
    • Vol. 25  (2) , 242-248
Abstract
Opiate receptor sites in the rat brain were defined in vivo by measuring the binding of etorphine, sufentanil, diprenorphine and naloxone in saturation and cross-competition experiments. The binding data were analyzed simultaneously, using a computerized curve-fitting technique with an extended least-squares nonlinear regression program. Three types of binding sites could be distinguished: site 1 (18 pmol/g brain), site 2 (15 pmol/g brain) and site 3 (20 pmol/g brain). Site 1 is bound selectively by sufentanil (the ratio of the apparent equilibrium dissociation constants K2/K1 .apprxeq. 1200), etorphine (K2/K1 .apprxeq. 20) and naloxone (K2/K1 .apprxeq. 15), and it resembles the .mu. binding site previously demonstrated in vitro. Diprenorphine binds to both site 1 and site 2 with high affinity and a slight (.apprx. 3.7-fold) selectivity for site 1 over site 2. The latter site may represent a mixture of the .delta. and .kappa. binding sites. The 3rd site displays relatively high affinity for naloxone, but it is clearly different from sites 1 and 2, as it exhibits a lack of affinity for sufentanil, etorphine and diprenorphine. This binding site population does not resemble any of the known opiate binding sites. Recent in vitro binding studies revealed that site 3 (now termed .lambda. site) is highly labile in vitro and was, therefore, not previously detected. These results suggest significant differences between in vitro and in vivo opioid receptor binding characteristics.