Neurons in the Rat Arcuate Nucleus Are Hyperpolarized by GABA&lt;sub&gt;B&lt;/sub&gt; and μ-Opioid Receptor Agonists: Evidence for Convergence at a Ligand-Gated Potassium Conductance

Loose, Michael D.; Rønnekleiv, Oline K.; Kelly, Martin J.

doi:10.1159/000125979

Cited by 65 publications

(42 citation statements)

References 22 publications

(28 reference statements)

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“…OFQ has recently been shown to activate a K¤ conductance in guinea-pig arcuate neurones (Wagner et al 1998), an effect similar to that reported earlier for DAMGO in arcuate neurones of the guinea-pig and rat (Loose & Kelly, 1990;Loose et al 1991). In the rat arcuate nucleus, application of OFQ (100-1000 nÒ) was found to activate an outward current (13·0 ± 1·5 pA, 43 of 78 cells) (Fig.…”

Section: Postsynaptic Modulation Of Hypothalamic Neuronessupporting

confidence: 85%

Pre‐ and postsynaptic actions of opioid and orphan opioid agonists in the rat arcuate nucleus and ventromedial hypothalamus in vitro

Emmerson

Miller

1999

The Journal of Physiology

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Using whole-cell patch clamp recording from neurones in an in vitro slice preparation, we have examined opioid-and orphanin FQ (OFQ)-mediated modulation of synaptic transmission in the rat arcuate nucleus and ventromedial hypothalamus (VMH). 2. Application of OFQ activated a Ba¥-sensitive and inwardly rectifying K¤ conductance in •50% of arcuate nucleus neurones and •95% of VMH neurones. The OFQ-activated current was blocked by the nociceptin antagonist [Phe 1

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Section: Postsynaptic Modulation Of Hypothalamic Neuronessupporting

confidence: 85%

Pre‐ and postsynaptic actions of opioid and orphan opioid agonists in the rat arcuate nucleus and ventromedial hypothalamus in vitro

Emmerson

Miller

1999

The Journal of Physiology

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“…It should be noted, however, that incubation time with insulin in previous studies was much shorter than in this study, and more detailed exploration of the possible involvement of GABA A receptor-mediated signaling in the insulin action on NPY gene expression is warranted. Approximately half of the neurons in the hypothalamus are GABAergic in vivo (Decavel and van den Pol, 1990), and GABA is shown to hyperpolarize most neurons in the arcuate nucleus (Loose et al, 1991;Wagner et al, 1998). In this study, we demonstrated that, as in vivo (Wisden et al, 1992;Schwartz et al, 1993;Kaupmann et al, 1997), GABA receptors are expressed in the hypothalamic slices and that most NPY neurons in the arcuate nucleus expressed GAD mRNA.…”

Section: Discussionsupporting

confidence: 49%

Insulin Inhibits Neuropeptide Y Gene Expression in the Arcuate Nucleus through GABAergic Systems

Sato¹,

Arima²,

Ozaki³

et al. 2005

J. Neurosci.

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Neuropeptide Y (NPY) in the arcuate nucleus is an orexigenic hormone of which levels are regulated by humoral as well as neural signals. In this study, we examined the regulation of NPY gene expression in the arcuate nucleus in hypothalamic organotypic cultures. Dexamethasone (DEX) (10 Ϫ9 to 10 Ϫ7 M) significantly increased NPY mRNA expression, and the effects were not influenced by coincubation with the sodium channel blocker tetrodotoxin (TTX), indicating that the action of DEX is independent of action potentials. Conversely, insulin (10 Ϫ11 to 10 Ϫ9 M) significantly inhibited NPY expression stimulated by DEX, and the inhibitory action of insulin was abolished in the presence of TTX. Because GABA and its receptors are expressed in the arcuate nucleus in vivo, we examined whether GABAergic systems were involved in the insulin action. The GABA B agonist baclofen significantly inhibited NPY expression stimulated by DEX, and the inhibitory action of insulin was completely abolished in the presence of either the GABA A antagonist bicuculline or the GABA B antagonist CGP35348 ( p-3-aminopropyl-p-diethoxymethyl phosphoric acid). Furthermore, increases in the GABA-synthesizing enzyme glutamic acid decarboxylase 65 (GAD65) mRNA expression preceded decreases in NPY mRNA expression in the arcuate nucleus in the cultures. Experiments in vivo also demonstrated that increases in GAD65 mRNA expression in the arcuate nucleus preceded decreases in the NPY mRNA expression in a fasting-refeeding paradigm and that intracerebroventricular injection of insulin increased GAD65 mRNA expression in the arcuate nucleus in fasted rats. These data suggest that insulin inhibits NPY gene expression in the arcuate nucleus through GABAergic systems.

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“…We therefore hypothesized that an elevation in serum estrogens plays a role in modifying the opioidergic tone through a modification of the receptor-mediated response in parvocellular neurosecretory neurons (e.g., P-endorphin, dopamine, and gonadotropin-releasing hormone). Since GABA is another potent inhibitory transmitter in the hypothalamus that is present in the ARC (Vincent et al, 1982) and the GABA, receptor is coupled to the same inwardly rectifying potassium conductance in the rat (Loose et al, 1991), we tested the hypothesis that estrogen suppresses both the p-opioid and GABA, responses that are coupled to the inwardly rectifying K+ channel. The EC,, values for the p-opioidand the GABA,-mediated hyperpolarization were compared in slices obtained from female guinea pigs exposed to low levels of serum estrogen versus high levels of serum estrogen.…”

Section: Morphinementioning

confidence: 99%

Estrogen suppresses mu-opioid- and GABAB-mediated hyperpolarization of hypothalamic arcuate neurons

1992

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The effects of estrogen on the response of hypothalamic arcuate neurons to mu-opioid and GABAB agonists were investigated. Intracellular recordings were made from arcuate neurons in slices prepared from ovariectomized guinea pigs that were pretreated with estrogen or vehicle. Estrogen shifted the dose-response curve to the mu-opioid agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol) by 3.4-fold; the EC50 for DAMGO was 240 +/- 25 nM in estrogen-treated females versus 70 +/- 12 nM in the controls. The maximal hyperpolarization induced by DAMGO was equivalent in neurons from both groups. The Ke for the naloxone antagonism of the DAMGO response was similar in both groups, which would indicate that the affinity of the mu-receptor was unchanged. To explore where in the receptor/G-protein/K+ channel cascade estrogen may be acting to attenuate the mu-opioid-mediated hyperpolarization, the response to the GABAB agonist baclofen was also tested. Estrogen treatment also shifted the dose-response curve for the baclofen-induced hyperpolarization by 3.3-fold without altering the maximum hyperpolarization; the EC50 shifted from 11.0 +/- 4.0 microM to 36.0 +/- 5.0 microM. All of the neurons were identified after linking the intracellular biocytin with streptavidin-FITC, and a subpopulation of cells in both groups were immunoreactive for beta-endorphin. We conclude that estrogen decreases the functional coupling of the mu- opioid and GABAB receptors to the inwardly rectifying K+ channel possibly through an action on the G-protein.

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Neurons in the Rat Arcuate Nucleus Are Hyperpolarized by GABA<sub>B</sub> and μ-Opioid Receptor Agonists: Evidence for Convergence at a Ligand-Gated Potassium Conductance

Cited by 65 publications

References 22 publications

Pre‐ and postsynaptic actions of opioid and orphan opioid agonists in the rat arcuate nucleus and ventromedial hypothalamus in vitro

Pre‐ and postsynaptic actions of opioid and orphan opioid agonists in the rat arcuate nucleus and ventromedial hypothalamus in vitro

Insulin Inhibits Neuropeptide Y Gene Expression in the Arcuate Nucleus through GABAergic Systems

Estrogen suppresses mu-opioid- and GABAB-mediated hyperpolarization of hypothalamic arcuate neurons

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