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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-11-5
pubmed:abstractText
We previously reported (see also the accompanying paper) that dynorphin A significantly enhanced the voltage-dependent K(+) M-current (I(M)) in CA3 and CA1 hippocampal pyramidal neurons (HPNs). Because the opioid-receptor-like-1 (ORL-1) receptor shares a high sequence homology with opioid receptors and is expressed in rat hippocampus, we examined the effects of orphanin FQ or nociceptin, the endogenous ligand for the ORL-1 receptor, using the rat hippocampal slice preparation and intracellular voltage-clamp recording. Current-voltage (I-V) relationships from CA1 HPNs revealed that nociceptin superfusion induced an outward current reversing near the equilibrium potential for K(+) ions. Ba(2+) (2 mM) blocked this effect. The nociceptin-induced current was largest at depolarized membrane potentials, where I(M) is largely activated. Nociceptin concentrations of 0.5-1 microM (but not 0.1 microM) significantly increased I(M) relaxation amplitudes with recovery on washout. Interestingly, both the general opiate antagonist naloxone and the kappa receptor antagonist nor-binaltorphimine (nBNI) inhibited the nociceptin-induced I(M) increases and outward currents in the depolarized range but not the inward current induced at hyperpolarized potentials. The putative ORL-1 receptor antagonist, [Phe(1)Psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2) (hereafter ORLAn), blocked most of the nociceptin current near rest but not the I(M) increase. However, ORLAn alone had direct effects similar to those of nociceptin, indicating that ORLAn might be a partial agonist. Our results suggest that nociceptin postsynaptically modulates the excitability of HPNs through ORL-1 and kappa-like opiate receptors linked to different K(+) channels.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
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
1776-85
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Nociceptin augments K(+) currents in hippocampal CA1 neurons by both ORL-1 and opiate receptor mechanisms.
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.