orexin receptor activity

Definition

Target type: molecularfunction

Combining with orexin to initiate a change in cell activity. [GOC:ai]

Orexin receptors, also known as hypocretin receptors, are G protein-coupled receptors that play a crucial role in regulating arousal, wakefulness, and appetite. They are activated by the neuropeptides orexin A and orexin B, which are produced in the hypothalamus. There are two main types of orexin receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Both receptors are expressed throughout the brain and in peripheral tissues, but they have distinct distributions and signaling properties.

**OX1R** is primarily expressed in the lateral hypothalamus, the perifornical area, the paraventricular nucleus, and the dorsal raphe nucleus. It is also found in the amygdala, hippocampus, and cortex. Activation of OX1R leads to the stimulation of the Gq/11 signaling pathway, resulting in the activation of phospholipase C (PLC), which in turn hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol trisphosphate (IP3). DAG activates protein kinase C (PKC), while IP3 mobilizes intracellular calcium. This cascade of events leads to the phosphorylation of downstream signaling molecules, ultimately resulting in increased neuronal excitability, arousal, and wakefulness.

**OX2R** is more widely distributed than OX1R, with high expression in the locus coeruleus, the ventrolateral periaqueductal gray, the dorsal raphe nucleus, and the substantia nigra. It also has a significant presence in the amygdala, hippocampus, and cortex. Activation of OX2R triggers the Gαs signaling pathway, leading to the stimulation of adenylyl cyclase and the subsequent production of cyclic adenosine monophosphate (cAMP). cAMP activates protein kinase A (PKA), which then phosphorylates various downstream targets, resulting in a variety of cellular effects, including the modulation of synaptic plasticity, neurotransmitter release, and gene expression.

**Overall, orexin receptor activity is essential for maintaining normal sleep-wake cycles, regulating energy homeostasis, and controlling appetite. Dysregulation of orexin signaling has been implicated in various neurological and psychiatric disorders, including narcolepsy, obesity, and addiction. Therefore, understanding the molecular function of orexin receptors is crucial for developing effective therapies for these conditions.**'
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Proteins (2)

Compounds (16)