Specific opiate receptors on isolated mammalian gastric smooth muscle cells

Abstract

The predominant opioid peptides of the gut, Met-enkephalin and Leu-enkephalin are confined to neurones of the myenteric plexus^1–4. Axonal projections from these neurones innervate the circular muscle layer running parallel to the smooth muscle cells⁵. An opioid tridecapeptide (dynorphin), first isolated from the porcine pituitary⁶, is found in neurones of the submucosal plexus in the guinea pig; axonal projections from these neurones also innervate the circular muscle layer^7,8. Dynorphin consists of an N-terminal Leu-enkephalin sequence coupled to a C-terminal octapeptide by an Arg–Arg sequence. Neural receptors for all three opioid peptides and for opiate narcotics have been identified in the myenteric plexus where they cause hyper-polarization of neurones^9,10, inhibition of acetylcholine (ACh) release¹¹ and blockade of muscle contraction induced by field stimulation^12–16. Measurements of motor activity in circular muscle where enkephalinergic fibres are most abundant, suggest that opiates also have a direct contractile action^17–20. We have tested this possibility hi isolated gastric smooth muscle cells devoid of neural elements^21,22, and report here the presence of specific high-affinity opiate receptors on such cells of the guinea pig. The receptors mediate contraction as measured by image-splitting micrometry, and exhibit a rank order of potency and absolute values similar to those reported for neural receptors of the myenteric plexus. In view of the distribution of enkephalinergic fibres predominantly to gut smooth muscle, our results strongly support a direct neuro- transmitter role for enkephalins in this region.