Related Experiment Video
Updated: May 9, 2026
09:29
Isolation of Targeted Hypothalamic Neurons for Studies of Hormonal, Metabolic, and Electrical Regulation
Published on: August 4, 2023
Orexin/hypocretin receptor signalling cascades.
1Biochemistry and Cell Biology, Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
British Journal of Pharmacology
|August 2, 2013
Summary
Orexin (hypocretin) receptor signaling is complex, influencing sleep, appetite, and reward. Understanding these diverse pathways is key for developing new treatments for sleep disorders, obesity, and addiction.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Orexin (hypocretin) peptides and their G-protein-coupled receptors are crucial for regulating sleep-wake cycles.
- These systems also significantly impact appetite, metabolism, stress, and reward pathways.
- Dysregulation is implicated in sleep disorders, obesity, and addiction, highlighting therapeutic potential.
Purpose of the Study:
- To review current knowledge on orexin receptor signaling cascades.
- To elucidate the diverse mechanisms and physiological targets of orexin receptor activation.
- To provide a foundation for understanding therapeutic interventions targeting these receptors.
Main Methods:
- Comprehensive literature review of orexin receptor signaling.
- Analysis of evidence regarding G-protein coupling and downstream effectors.
- Evaluation of studies on central nervous system and cellular responses.
Main Results:
- Orexin receptor signaling is more multifaceted than previously understood, involving at least three G-protein families.
- Receptors regulate ion channels, phospholipases, adenylyl cyclase, and various kinases.
- Central nervous system effects include neuroexcitation, neurotransmitter release modulation, and synaptic plasticity.
- Calcium signaling is significantly influenced via multiple pathways, and prolonged stimulation can induce cell death in certain cell types.
Conclusions:
- Orexin receptor signaling pathways are highly diverse and context-dependent.
- This complexity offers significant therapeutic opportunities for a range of conditions.
- Further research into specific signaling cascades and tissue responses is warranted.
Related Concept Videos
01:24Intracellular Signaling Cascades
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
01:24Intracellular Signaling Cascades
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:22Opioid Receptors: Overview
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...