Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-11-5
pubmed:abstractText
Most electrophysiological studies of opioids on hippocampal principal neurons have found indirect actions, usually through interneurons. However, our laboratory recently found reciprocal alteration of the voltage-dependent K(+) current, known as the M-current (I(M)), by kappa and delta opioid agonists in CA3 pyramidal neurons. Recent ultrastructural studies have revealed postsynaptic delta opiate receptors on dendrites and cell bodies of CA1 and CA3 hippocampal pyramidal neurons (HPNs). Reasoning that previous electrophysiological studies may have overlooked voltage-dependent postsynaptic effects of the opioids in CA1, we reevaluated their role in CA1 HPNs using the rat hippocampal slice preparation for intracellular current- and voltage-clamp recording. None of the delta and mu; receptor-selective opioids tested, including [D-Pen(2,5)]-enkephalin (DPDPE), [D-Ala(2)]-deltorphin II (deltorphin), [D-Ala(2), NMe-Phe(4), Gly-ol]-enkephalin (DAMGO), and [D-Ala(2), D-Leu(5)] enkephalin (DADLE), altered membrane properties such as I(M) or Ca(2+)-dependent spikes in CA1 HPNs. The nonopioid, Des-Tyr-dynorphin (D-T-dyn), also had no effect. By contrast, dynorphin A (1-17) markedly increased I(M) at low concentrations and caused an outward current at depolarized membrane potentials. The opioid antagonist naloxone and the kappa receptor antagonist nor-binaltorphimine (nBNI) blocked the I(M) effect. However, the kappa-selective agonists U69,593 and U50,488h did not significantly alter I(M) amplitudes when averaged over all cells tested, although occasional cells showed an I(M) increase with U50,488h. Our results suggest that dynorphin A postsynaptically modulates the excitability of CA1 HPNs through opiate receptors linked to voltage-dependent K(+) channels. These findings also provide pharmacological evidence for a functional kappa opiate receptor subtype in rat CA1 HPNs but leave unanswered questions on the role of delta receptors in CA1 HPNs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3,4-Dichloro-N-methyl-N-(2-(1-pyrrol..., http://linkedlifedata.com/resource/pubmed/chemical/Benzeneacetamides, http://linkedlifedata.com/resource/pubmed/chemical/Dynorphins, http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, D-Penicillamine (2,5)-, http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, Leucine-2-Alanine, http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, delta, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, kappa, http://linkedlifedata.com/resource/pubmed/chemical/U 69593, http://linkedlifedata.com/resource/pubmed/chemical/deltorphin, http://linkedlifedata.com/resource/pubmed/chemical/dynorphin (2-17)
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3077
pubmed:author
pubmed:issnType
Print
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1768-75
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10515966-3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-ben..., pubmed-meshheading:10515966-Animals, pubmed-meshheading:10515966-Benzeneacetamides, pubmed-meshheading:10515966-Dynorphins, pubmed-meshheading:10515966-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, pubmed-meshheading:10515966-Enkephalin, D-Penicillamine (2,5)-, pubmed-meshheading:10515966-Enkephalin, Leucine-2-Alanine, pubmed-meshheading:10515966-Hippocampus, pubmed-meshheading:10515966-Oligopeptides, pubmed-meshheading:10515966-Peptide Fragments, pubmed-meshheading:10515966-Potassium Channels, pubmed-meshheading:10515966-Pyramidal Cells, pubmed-meshheading:10515966-Pyrrolidines, pubmed-meshheading:10515966-Rats, pubmed-meshheading:10515966-Receptors, Opioid, pubmed-meshheading:10515966-Receptors, Opioid, delta, pubmed-meshheading:10515966-Receptors, Opioid, kappa
pubmed:year
1999
pubmed:articleTitle
Dynorphin selectively augments the M-current in hippocampal CA1 neurons by an opiate receptor mechanism.
pubmed:affiliation
The Scripps Research Institute, Department of Neuropharmacology, La Jolla, California 92037, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.