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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 at 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 KD; 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.