The sub cellular localization of stereo specific opiate binding in mouse brain

Of the three primary sub cellular fractions derived from mouse brain homogenates, the P₃ (microsomal) fraction binds ³H di hydromorphine stereo specifically with the highest capacity per mg. of protein; this level is nearly as great as that bound by purified synaptosomal plasma membranes (SPM). The binding to P₃ is unlikely to be attributable to contamination with SPM, because a) ten times as much total binding is recovered in P₃ as in SPM, and b) the level of binding to P₃ is highest in a sub fraction banding above 0.8 M sucrose, rich in surface membranes of all types, whereas SPM bands preferentially at 0.8-1.1 M sucrose. The binding of either ³H di hydromorphine or ³H naloxone to P₃ is, however, indistinguishable from that found in nerve endings with respect to a) its K(D); b) the relative potencies of several agonists in displacing it; and c) the effects on it of Na⁺ or trypsin. Thus, it appears that stereo specific opiate receptors are distributed diffusely on the entire surface of nerve cells and not concentrated at the synaptic region as has previously been supposed.