title: Opioid-mediated modulation of calcium currents in striatal and pallidal neurons following reserpine treatment: focus on kappa response.
abstract: Previous work has shown that enkephalins target N-type calcium (Ca2+) channels in striatal and globus pallidus (GP) neurons, principally through activation of mu-like receptors. Here, we examined the effects of selective mu, delta, and kappa agonists on Ca2+ currents in striatal and GP neurons isolated from either control or reserpine-treated rats. In cells from control rats DAMGO and dynorphin (DYN) inhibited high-voltage-activated (HVA) Ca2+ currents preferentially in "medium-to-small" GP cells (likely to correspond to parvalbumin-negative cells). The kappa response was elicited by several agonists (DYN 17, DYN 13, BRL, U50-488-H), U50-488-H being the most effective (>30% maximal inhibition). U50-488-H affected both omega-CgTxGVIA-sensitive and nimodipine-sensitive Ca2+ conductances. The kappa-mediated effect (but not the mu response) was slow and blocked by chelerythrine, supporting the involvement of protein kinase C. In neurons from reserpinized rats we observed modest changes in the mu-inhibited fraction in small GP cells and a dramatic reduction of the kappa-sensitive fraction in principal striatal cells. These data imply that aminergic depletion alters opiate transmission differentially in the indirect and direct pathways. The suppression of the kappa response only in striatum reinforces the notion of an imbalance of endogenous opiates as relevant in extrapyramidal motor dysfunctions.
authors.affiliation: Dipartimento di Neuroscienze, Università di Roma Tor Vergata, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Spadoni
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Martella
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martorana
authors.forename: Franco
authors.initials: F
authors.lastname: Lavaroni
authors.forename: Vincenza
authors.initials: V
authors.lastname: D'Angelo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000470:Alkaloids; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D053119:Benzophenanthridines; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004399:Dynorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010617:Phenanthridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000470:Alkaloids; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D053119:Benzophenanthridines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D010617:Phenanthridines; D017473:Receptors, Opioid, kappa; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C051844:norbinaltorphimine; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; D012110:Reserpine; D020866:omega-Conotoxin GVIA; C016299:chelerythrine