Nigral 6-hydroxydopamine lesions equally decrease mu and delta opiate binding to striatal patches: further evidence for a conformationally malleable type 1 opiate receptor.

We have investigated the effect of nigral 6-hydroxydopamine (6-OHDA) lesions on binding of the mu receptor ligand dihydromorphine (DHM) and the delta receptor ligand [D-Ala2, D-Leu5]-enkephalin (DADLE) to sections of rat striatum under conditions which yield mu-like and delta-like ligand selectivities at discrete receptor patches (Type 1 receptor). 3H-DHM binding was decreased 43% while 3H-DADLE was decreased 22%. However, when the contribution of diffuse binding (Type 2) which is not affected by 6-OHDA is subtracted from the patch, the decrease is approximately 49% for both ligands. These data support the hypothesis that the Type 1 receptor of striatal patches is a conformationally malleable receptor entity which can exist in states having high affinities for various classes of opiate ligands.