The actions of the kappa 1 opioid agonist U-50,488 on presynaptic nerve terminals of the chick ciliary ganglion.
The actions of the kappa 1 opioid receptor agonist U-50,488 (trans-(+-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benz ene - acetamide methane sulfonate) on the membrane properties of presynaptic calyciform nerve terminals of the chick ciliary ganglion were examined using intracellular recordings obtained from intact ganglion preparations maintained in vitro. U-50,488 produced a concentration-dependent (30-1000 microM) hyperpolarization with an apparent increase in input resistance. This hyperpolarization resulted from inhibition of the Na(+)-K+ inward rectifier, since it was blocked by 3 mM Cs+ and was not observed when terminals were depolarized beyond resting potential where inward rectification was voltage inactivated. A depolarizing effect on membrane potential with a further rise in input resistance was commonly observed at the highest perfused U-50,488 concentration (1 mM). The depolarizing event appears to result from a decrease in membrane potassium conductance, as the reversal potential for the response was estimated to be between -70 and -90 mV and the potassium channel blocker Ba2+ (1 mM) abolished the response. The kappa 1 opioid receptor agonist also blocked spontaneously occurring miniature hyperpolarizations in the terminals, which are considered to be due to a Ca(2+)-dependent K+ conductance. Most of the responses to U-50,488 were abolished in the presence of the kappa 1 receptor antagonist norbinaltorphimine. In conclusion, the excitability of presynaptic nerve terminals in the chick ciliary ganglion can be modulated by the inhibition of at least three separate ion conductances following activation of kappa 1 opioid receptor sites in the nerve terminal region.
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, MO 63104.
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Fletcher
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Chiappinelli
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002645:Chickens; D004594:Electrophysiology; D005726:Ganglia, Parasympathetic / Q000166:cytology* / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D015222:Sodium Channels / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*
D000700:Analgesics; D015221:Potassium Channels; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D015222:Sodium Channels; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer