Evidence for two separate opiate peptide neuronal systems

WHEN Hughes et al.1 first described the sequences of the enkephalins, they pointed out that methionine–enkephalin (met-enkephalin) could be found in β-lipotropin (β-LPH 61–65). The entire C-terminal fragment of β-LPH was subsequently found to have opiate-like properties (β-LPH 61–91 or β-endorphin)2–7, and it seemed reasonable to hypothesise that the primary biosynthetic route for met-enkephalin was β-LPH to β-endorphin and eventually to met-enkephalin. Although this hypothesis awaits biochemical evidence, immunocytochemical studies of these peptides may shed light on the question. If β-LPH and β-endorphin are, in fact, enkephalin precursors which are stored by enkephalinergic neurones, one would expect them to be visualised in met-enkephalin-positive cells. Several laboratories produced immunocytochemical maps of the distribution of enkephalin-like-immunoreactivity (enkephalin-reactivity) in mammalian brain8–11. Watson et al.12 demonstrated β-LPH-reactive cells and processes in rat brain. This β-LPH reactivity has the same distribution as β-endorphin-like-immunoreactivity (β-endorphin-reactivity) as reported by Bloom et al.13 and Watson et al.14. However, the distribution of the ) β-LPH/β-endorphin-reactive system on the one hand and the met-enkephalin-reactive system on the other seemed quite different. Met-enkephalin-reactivity was seen in many local cell groups throughout the neuraxis, especially the lower brain stem8–11, whereas β-LPH- and β-endorphin-reactivities were found only in a single hypothalamic cell group with long ascending and descending processes12–14. We present here biochemical and anatomical evidence for the existence of two separate opioid systems in brain—an enkephalin system and a β-LPH/β-endorphin system. We also present immunocytochemical data for the coexistence in the brain of ACTH with β-LPH/β-endorphin.