Orexin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on [43]) are activated endogenous polypeptides orexin-A and orexin-B (also known hypocretin-1 -2; 33 28 aa) derived from a common precursor, preproorexin or orexin proteolytic cleavage some typical peptide modifications [117]. signaling has been associated with regulation of sleep wakefulness, reward addiction, appetite feed...

orexin, mainly produced by orexin-expressing neurons in the lateral hypothalamus (lh), plays an important role in pain modulation. moreover, it is shown that the nucleus accumbens (nac) is one of the important areas involved in this modulation. orexin-1 (ox1) and orexin-2 (ox2) receptors are densely distributed in the nac. the study investigated the involvement of ox1 receptors in the nac on an...

In this study, we have compared the abilities of orexin-A and orexin-B and variants of orexin-A to activate different Ca(2+) responses (influx and release) in human OX(1) and OX(2) receptor- expressing Chinese hamster ovary cells. Responses mediated by activation of both receptor subtypes with either orexin-A or -B were primarily dependent on extracellular Ca(2+), suggesting similar activation ...

Orexin signaling is essential for normal regulation of arousal and behavioral state control and represents an attractive target for therapeutics combating insomnia. Alternatively termed hypocretins, these neuropeptides were named to reflect sequence similarity to incretins and their potential to promote feeding. Current nomenclature reflects these molecular and biochemical discovery approaches ...

Following inducible expression in HEK293 cells, the human orexin-1 receptor was targeted to the cell surface but became internalized following exposure to the peptide agonist orexin A. By contrast, constitutive expression of the human cannabinoid CB1 receptor resulted in a predominantly punctate, intracellular distribution pattern consistent with spontaneous, agonist-independent internalization...

Orexin A and B (hypocretin 1 and 2) are the endogenous ligands of orexin receptors, a G-protein-coupled orphan receptor family containing orexin 1 (OX1) and orexin 2 (OX2) types. Orexin A induces analgesia in acute and inflammatory pain models. We further elucidated the possible antiallodynic effect of intrathecal orexins in a rat model of postoperative pain. Mechanical allodynia was induced by...

Both orexin and neurotensin are expressed in the lateral hypothalamic area (LHA) and have been implicated in the regulation of feeding, motor activity and the reward system. A double label immunofluorescence and in situ hybridization studies showed that neurotensin colocalizes with orexin in neurons of the LHA. Pharmacological studies suggested that neurotensin excites orexin-producing neurons ...

Numerous studies have demonstrated the ability of orexin-A to regulate adrenocortical cells through the mitogen-activated protein kinase signaling pathway. In the present study, human H295R adrenocortical cells were exposed to orexin‑A (10‑10-10‑6 M), with orexin receptor type 1 (OX1 receptor) antagonist SB334867 or AKT antagonist PF‑04691502. It was found that orexin‑A stimulated H295R cell pr...

Orexin neuropeptides promote arousal, appetite, reward, and energy expenditure. However, whether orexin affects bone mass accrual is unknown. Here, we show that orexin functions centrally through orexin receptor 2 (OX2R) in the brain to enhance bone formation. OX2R null mice exhibit low bone mass owing to elevated circulating leptin, whereas central administration of an OX2R-selective agonist a...

The activity of dopamine (DA)-containing neurons in the ventral tegmental area (VTA) is a key mechanism in mesolimbic reward processing that has modulatory effects on different diencephalic structures like hippocampus (HIP), and receives inhibitory feedback and excitatory feed forward control. In addition, within the hippocampus, DA receptors are mostly located in the dorsal part (CA1) and dopa...