Opioid inhibition of synaptic transmission in the guinea-pig myenteric plexus.
Intracellular recordings were made from neurones in the myenteric plexus of the guinea-pig ileum. Presynaptic nerves were excited by a focal stimulating electrode on an interganglionic strand. Fast excitatory postsynaptic potentials (e.p.s.ps) were depressed in amplitude by morphine and [Met5]enkephalin in the concentration range of 1 nM-1 microM. Nicotinic depolarizations evoked by exogenously applied acetylcholine (ACh) were not affected by these opioids. Hyperpolarization of the presynaptic fibres probably contributed to the depression of the fast e.p.s.p. because fast e.p.s.ps evoked by low stimulus voltages were more depressed than those evoked by high stimulus voltages and fast e.p.s.ps resulting from activation of a single presynaptic fibre were blocked in a non-graded manner. Opioids depressed the slow e.p.s.p. in those neurones in which they did not change the resting membrane potential. The slow e.p.s.p. was increased in amplitude in those neurones hyperpolarized by opioids. Depolarizations resulting from application of barium, substance P or ACh were also enhanced by opioids. Equivalent circuit models in which opioids increase, and substance P or ACh decrease, the same potassium conductance could account for this enhancement. The actions of opioids were prevented or reversed by naloxone (1 nM-1 microM). It is concluded that morphine and enkephalin inhibit the release of ACh and a non-cholinergic transmitter from fibres of the myenteric plexus, and that this may involve a hyperpolarization of presynaptic fibres. Additionally, opioids can interact postsynaptically with other substances which affect membrane potassium conductances.
E
E
Cherubini
K
K
Morita
R A
RA
North
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001464:Barium / Q000494:pharmacology; D004553:Electric Conductivity; D004723:Endorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004744:Enkephalin, Methionine / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation; D009020:Morphine / Q000494:pharmacology; D009197:Myenteric Plexus / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
D004723:Endorphins; D001464:Barium; D013373:Substance P; D009270:Naloxone; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D009538:Nicotine; D009020:Morphine; D000109:Acetylcholine; D011188:Potassium