Hypocretin‐1 causes G protein activation and increases ACh release in rat pons

@article{Bernard2003Hypocretin1CG,
  title={Hypocretin‐1 causes G protein activation and increases ACh release in rat pons},
  author={René Bernard and Ralph Lydic and Helen A. Baghdoyan},
  journal={European Journal of Neuroscience},
  year={2003},
  volume={18}
}
The effects of the arousal‐promoting peptide hypocretin on brain stem G protein activation and ACh release were examined using 16 adult Sprague‐Dawley rats. In vitro[35S]GTPγS autoradiography was used to test the hypothesis that hypocretin‐1‐stimulated G protein activation is concentration‐dependent and blocked by the hypocretin receptor antagonist SB‐334867. Activated G proteins were quantified in dorsal raphe nucleus (DR), locus coeruleus (LC) and pontine reticular nucleus oral part (PnO) and… 

Hypocretin (Orexin) Receptor Subtypes Differentially Enhance Acetylcholine Release and Activate G Protein Subtypes in Rat Pontine Reticular Formation

TLDR
Data provided provide the first evidence that hypocretin receptors in rat PnO signal via inhibitory and stimulatory G proteins and that ACh release in rat pnO is modulated by hcrt-r2 and hcrT-r1.

Pontine reticular formation (PnO) administration of hypocretin-1 increases PnO GABA levels and wakefulness.

TLDR
Hypocretin-1 may promote wakefulness, at least in part, by increasing GABAergic transmission in the PnO, and this study tested this hypothesis using adult male Crl:CD (SD)IGS BR (Sprague-Dawley) rats.

GABAA receptors inhibit acetylcholine release in cat pontine reticular formation: implications for REM sleep regulation.

TLDR
The finding that A Ch release in the PRF is modulated by GABAA receptors is consistent with the interpretation that inhibition of GABAergic transmission in thePRF contributes to the generation of REM sleep, in part, by increasing pontine ACh release.

Anxiolytic function of the orexin 2/hypocretin A receptor in the basolateral amygdala

OX1 Orexin Receptors Couple to Adenylyl Cyclase Regulation via Multiple Mechanisms*

TLDR
It is concluded that OX1 receptors stimulate adenylyl cyclase via a low potency Gs coupling and a high potency phospholipase C → PKC coupling and the former or some exogenous Gs activation is essentially required for the PKC to significantly activate adenyll cyclase.

State-Dependent Interactions between Excitatory Neuromodulators in the Neuronal Control of Breathing

TLDR
This work explored the state-dependent functional interactions between three excitatory neuromodulators acting on neurokinin1 (NK1), α1 noradrenergic (α1 NE), and 5-HT2 serotonin receptors within the pre-Bötzinger complex (pre- BötC), an area critical for the generation of breathing.

Orexin/hypocretin receptor signalling cascades

TLDR
The evidence suggests that orexin receptor signalling is multifaceted, substantially more diverse than originally thought, and highly tunable, depending on the milieu in which they are operating.

References

SHOWING 1-10 OF 105 REFERENCES

Hypocretin-1 activates G proteins in arousal-related brainstem nuclei of rat

TLDR
The finding that hcrt-1 stimulated [35S]GTP&ggr;S binding suggests that some hCrt receptors in pontine brain stem couple to inhibitory G proteins, which is the first study to quantify and localize hcrT-1-induced G protein activation in specific brain stem nuclei.

Differential cholinergic activation of G proteins in rat and mouse brainstem: Relevance for sleep and nociception

TLDR
In the same pontine reticular formation area of B6 mouse where in vitro treatment with carbachol activates G proteins, in vivo microinjection of cholinomimetics causes a rapid eye movement sleep‐like state.

Effects of orexin (hypocretin) on GIRK channels.

TLDR
It is shown that orexins suppress G-protein-coupled inward rectifier (GIRK) channel activity, and this suppression is likely to lead to neuronal excitation, which may be one of the cellular mechanisms for the regulation of brain nuclei that are crucial for arousal, sleep, and appetite.

Selective Enhancement of Synaptic Inhibition by Hypocretin (Orexin) in Rat Vagal Motor Neurons: Implications for Autonomic Regulation

TLDR
Findings indicate that the hypocretin peptides can modulate and coordinate visceral autonomic output by acting directly on central vagal circuits.

Hypocretin-1 Modulates Rapid Eye Movement Sleep through Activation of Locus Coeruleus Neurons

TLDR
It is proposed that hcrt receptor 1 in the LC is a key target for REM sleep regulation and might be involved in the pathophysiological mechanisms of narcolepsy.

Carbachol Stimulates [35S]Guanylyl 5′-(γ-Thio)-Triphosphate Binding in Rapid Eye Movement Sleep-Related Brainstem Nuclei of Rat

TLDR
The activation of G-proteins by carbachol was concentration-dependent and antagonized by atropine, demonstrating that G- Proteins were activated via mAChR stimulation, and provides the first direct measures of mA ChR-activated G-Proteins in brainstem nuclei known to contribute to REM sleep generation.

Orexins/hypocretins excite rat sympathetic preganglionic neurons in vivo and in vitro.

TLDR
Results from the in vivo and in vitro studies together with the previous observation of the presence of orexin A-immunoreactive fibers in the IML suggest that orexins, when released within the IML, augment sympathetic outflow by acting directly on SPNs.

SB‐334867, a selective orexin‐1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin‐A in rats

TLDR
The view that orexin‐A is involved in the regulation of feeding patterns and that this influence is mediated through the orexIn‐1 receptor is strongly supported.
...