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Hyperpolarisation and depression of slow synaptic inhibition by enkephalin in frog sympathetic ganglion

Naturevolume 277pages5354 (1979) | Download Citation



EVIDENCE is accumulating to support the concept that the pentapeptides Met-enkephalin and Leu-enkephalin, the endogenous ligands for the opiate receptor, function as neuromodulators or neurotransmitters1,2. In the central nervous system the effects of enkephalins are complex and difficult to analyse, and their mode of action at the neuronal membrane level is still poorly understood. The most prominent action of enkephalins in the mammalian brain is depression of neuronal firing rate and it has been suggested that these peptides are inhibitory transmitters1,2. An increase in firing rate by enkephalins has, however, also been reported3. The response of central neurones to several putative transmitter substances is depressed or enhanced by enkephalins, suggesting a postsynaptic action4,5. It has also been shown that enkephalins suppress the K+-induced release of noradrenaline6, dopamine7 and acetylcholine7 from rat brain slices, indicating a presynaptic effect. The firing of myenteric neurones in the guinea-pig ileum is inhibited by enkephalins. This inhibition is probably due to a direct postsynaptic action of the enkephalins resulting in a hyperpolarisation of the neuronal membrane8. Most of the effects of enkephalins are antagonised by the specific opiate antagonist naloxone. Morphine produces effects very similar to those of enkephalins. Because of the possible role of enkephalins in inhibitory synaptic transmission, we studied the effects of Met-enkephalin on slow synaptic inhibition in frog sympathetic ganglion. We report here that Met-enkephalin causes a depression of the slow inhibitory postsynaptic potential (i.p.s.p.), probably mainly by a presynaptic action, and induces a hyper-polarisation of the ganglionic neurones. Both effects are antagonised by naloxone.

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  1. Institute of Veterinary Pharmacology and Toxicology, University of Utrecht, Biltstraat 172, 3572 BP, Utrecht, The Netherlands



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