The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Orexin Receptor Type-1 Couples Exclusively to Pertussis Toxin-Insensitive G-Proteins, While Orexin Receptor Type-2 Couples to Both Pertussis Toxin-Sensitive and -Insensitive G-Proteins
Open accessAbstract
Signal transduction pathways of orexin receptors were examined using a nerve-like cell line transfected with orexin receptor type-1 (OX1R) and orexin receptor type-2 (OX2R). Forskolin-stimulated cyclic adenosine 3,5-monophosphate (cAMP) accumulation in OX2R-expressing cells was inhibited by orexin in a dose-dependent manner, and the effect was abolished by pretreatment with pertussis toxin (PTX). The inhibitory effect of orexin on forskolin-stimulated cAMP accumulation was not observed in OX1R-expressing cells. Administration of orexin to these cells resulted in a transient increase of intracellular calcium concentration ([Ca(2+)](i)). Orexin-stimulated increases in [Ca(2+)](i) in OX1R- or OX2R-expressing cells were not affected by the PTX pretreatment. These observations suggest that OX1R couples exclusively to PTX-insensitive G-proteins, while OX2R couples to both PTX-sensitive and -insensitive G-proteins. To examine the relative contributions of these G-proteins in OX2R-mediated activation of neurons, we used histaminergic tuberomammillary nucleus neurons, in which OX2R is abundantly expressed. We found that a phospholipase C (PLC)-inhibitor, U73122, inhibits orexin-mediated neuronal activation, but PTX showed no effect on it. This suggests that although OX2R couples to multiple G-proteins, activation of neurons by orexins through OX2R is mediated via a PTX-insensitive, PLC dependent pathway.
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Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R. M., Tanaka, H., Williams, S. C., Richardson, J. A., Kozlowski, G. P., Wilson, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80949-6 · Cited by 5,501
Self-citationThe hypocretins: hypothalamus-specific peptides with neuroexcitatory activity
de Lecea, L., Kilduff, T. S., Peyron, C., Gao, X.-B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.322 · Cited by 3,878
Neurons containing hypocretin (orexin) project to multiple neuronal systems
Peyron, C., Tighe, D. K., van den Pol, A. N., de Lecea, L., Heller, H. C., Sutcliffe, J. G., & Kilduff, T. S. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-23-09996.1998 · Cited by 3,466
Narcolepsy in orexin Knockout Mice
Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., Richardson, J. A., Williams, S. C., Xiong, Y., Kisanuki, Y., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)81973-x · Cited by 3,095
Differential expression of orexin receptors 1 and 2 in the rat brain
Marcus, J. N., Aschkenasi, C. J., Lee, C. E., Chemelli, R. M., Saper, C. B., Yanagisawa, M., & Elmquist, J. K. (2001) · Journal of Comparative Neurology · doi:10.1002/cne.1190 · Cited by 1,659
Cited by
The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness
Sakurai, T. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2092 · Cited by 1,276
Self-citationBorgland, S. L., Taha, S. A., Sarti, F., Fields, H. L., & Bonci, A. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.016 · Cited by 718
Role of orexin/hypocretin in reward-seeking and addiction: Implications for obesity
Cason, A. M., Smith, R. J., Tahsili-Fahadan, P., Moorman, D. E., Sartor, G. C., & Aston-Jones, G. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.03.009 · Cited by 229
The discovery of suvorexant, the first orexin receptor drug for insomnia
Coleman, P. J., Gotter, A. L., Herring, W. J., Winrow, C. J., & Renger, J. J. (2017) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104837 · Cited by 128
Brown, R. M., Khoo, S. Y.-S., & Lawrence, A. J. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145713000333 · Cited by 101
Metadata
- Authors
- Zhu, Y., Miwa, Y., Yamanaka, A., Yada, T., Shibahara, M., Abe, Y., Sakurai, T., & Goto, K.
- Venue
- Journal of Pharmacological Sciences
- Publisher
- Japanese Pharmacological Society
- Published
- 2003
- Volume
- 92
- Issue
- 3
- Pages
- 259-266
- ISSN
- 1347-8613 (ISSN-L)
- 1347-8648
- OpenAlex
- W1967866139
- Cited by
- 173
- References
- 5
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Orexin Receptor Type-1 Couples Exclusively to Pertussis Toxin-Insensitive G-Proteins, While Orexin Receptor Type-2 Couples to Both Pertussis Toxin-Sensitive and -Insensitive G-Proteins. https://app.cochat.ai/papers/10.1254/jphs.92.259
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- Zhu, Y., Miwa, Y., Yamanaka, A., Yada, T., Shibahara, M., Abe, Y., Sakurai, T., & Goto, K. (2003). Orexin Receptor Type-1 Couples Exclusively to Pertussis Toxin-Insensitive G-Proteins, While Orexin Receptor Type-2 Couples to Both Pertussis Toxin-Sensitive and -Insensitive G-Proteins. Journal of Pharmacological Sciences. https://doi.org/10.1254/jphs.92.259
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