Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides.

Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. Research Abstract Details 

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Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. Abstract Text:

Ying Li,Anthony N van den Pol,

The hypocretin/orexin arousal system plays a key role in maintaining an alert wake state. The hypocretin peptide is colocalized with an opioid peptide, dynorphin. As dynorphin may be coreleased with hypocretin, we asked what action simultaneous stimulation with the excitatory neuropeptide hypocretin and the inhibitory peptide dynorphin might exert on cells postsynaptic to hypocretin axons, including hypocretin neurons. Hypocretin neurons received direct synaptic contact from other hypocretin neurons but showed little direct response to hypocretin. Here, we show that mouse hypocretin neurons are acutely sensitive to dynorphin. Dynorphin inhibits the hypocretin system by direct postsynaptic actions (hyperpolarization, decreased spike frequency, increased GIRK (G-protein-gated inwardly rectifying K+ channel) current, and attenuated calcium current, and indirectly by reducing excitatory synaptic tone. Interestingly, a selective antagonist of kappa-opioid receptors enhanced activity of the hypocretin system, suggesting ongoing depression by endogenous hypothalamic opioids. Electrical stimulation of hypothalamic microslices that contained hypocretin cells and their axons evoked dynorphin release. Costimulation with dynorphin and hypocretin had three different effects on neurons postsynaptic to hypocretin axons: direct response to only one or the other of the two peptides [hypocretin cells respond to dynorphin, arcuate neuropeptide Y (NPY) cells respond to hypocretin], differential desensitization causing shift from inhibitory current to excitatory current with repeated coexposure (melanin-concentrating hormone neurons), synergistic direct excitation by hypocretin and presynaptic attenuation of inhibition by dynorphin (arcuate NPY neurons). These results suggest that hypocretin neurons may be able to exercise a high degree of modulatory control over postsynaptic targets using multiple neuropeptides with target-dependent actions.

Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. Publishing Authors By Initials

Y Li,AN van den Pol,

For similar peptides: neuropeptides research abstracts see: peptides: neuropeptides research

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Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of neuroscience : the official journal

VOLUME: 26

Page Numbers: 13037-47

Journal Abbreviation: J. Neurosci.

ISSN: 1529-2401

DAY: 13

MONTH: Dec

YEAR: 2006

Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8102140

Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. Keywords Mesh Terms:

KEYWORDS: Neuropeptides

MESH TERMS: physiology

Chemical & Substance for Abstract: Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. Information

Substance Name: Dynorphins

Registry Number: 74913-18-1

Grant and Affiliation Information for Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides.

AFFILIATION: Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS48476

ACRONYM: NS

MEDLINETA: J Neurosci

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