Abstract
Present evidence indicates that there are two independent peptidergic systems: One is characterized by the presence of the short-chain peptides, methionine-enkephalin and leucine-enkephalin and is widespread throughout the central and peripheral nervous systems whereas the other system contains the long-chain peptide, β-endorphin and is centred around the hypothalamuspituitary axis with extensions into the thalamus and midline region of the midbrain. The question arises of whether or not the long and short opioid peptides interact with several receptors subserving different physiological functions. This problem has been investigated by using four parallel assays: the depression of contractions of the guinea-pig ileum and of the mouse vas deferens and the inhibition of binding of [3H]-naloxone and of [3H]-leucine-enkephalin in brain homogenates. Ovine β- endorphin is approximately equipotent in the guinea-pig ileum and mouse vas deferens. Methionineenkephalin is about as potent as β-endorphin in the guinea-pig ileum while, in the mouse vas deferens, it is more active; Leucine-enkephalin is slightly more potent than methionine-enkephalin in the mouse vas deferens but less active in the guinea-pig ileum. In contrast, morphine is much les potent in the mouse vas deferens than in the guinea-pig ileum. The binding sites in the brain represented by [3H]-leucine-enkephalin are quite different from those represented by [3H]-naloxone. It would appear that the pharmacological responses of the guinea-pig ileum to the peptides and morphine are more closely related to their abilities to inhibit [3H]-naloxone binding than [3H]-leucine-enkephalin binding while the pharmacological responses in the mouse vas deferens are more related to the inhibition of [3]-leucine-enkephalin than of [3H]-naloxone binding.
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