Interaction of Putative Opioid Peptides with Opiate Receptors

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Abstract
Binding of 3H‐enkephalinamide and 3H‐naloxone to P2‐fractions of whole rat brain homogenate displayed saturable, stereospecific binding to receptor sites with at least two binding sites for 3H‐met‐enkephalinamide (type I: KD = 0.4 nM and Bmax = 35 fmol/mg protein; type II: KD = 5.7 nM and Bmax = 57 fmol/mg protein) and for 3H‐naloxone (type I: KD = 1.5 nM and Bmax = 40 fmol/mg protein; type II: KD = 51 nM and Bmax = 255 fmol/mg protein), β‐endorphin and met‐ and leu‐enkephalin produced a concentration‐dependent inhibition of 3H‐met‐enkephalinamide and 3H‐naloxone binding with dissociation constants in the nanomolar range, but with very different displacement curves. Purified porcine ACTH (1–39) displaced both 3H‐met‐enkephalinamide and 3H‐naloxone with dissociation constants of 3.4 × 10‐ M and 1.8 × 10−6 M, respectively. The synthetic congeners, ACTH (1–32) and to a lesser extent ACTH (1–28) and ACTH (1–24) showed a similar effect, whereas other fragments of ACTH were inactive in concentrations ranging from 10−10 to 10−6 M. In the same concentration range cholecystokinin congeners (CCK‐8 and CCK‐4) were without effect. Since ACTH immunoreactive nerves seem also to contain β‐endorphin and furthermore, to show a partially overlapping distribution with the enkephalinergic systems it is possible that the binding of ACTH fragments to opiate receptors is of physiological relevance.