Choline-Sigma-1R as an Additional Mechanism for Potentiation of Orexin by Cocaine
Orexin A, an endogenous peptide involved in several functions including reward, acts via activation of orexin receptors OX and OX , Gq-coupled GPCRs. We examined the effect of a selective OX agonist, OXA (17-33) on cytosolic calcium concentration, [Ca ] , in neurons of nucleus accumbens, an importan...
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Veröffentlicht in: | International journal of molecular sciences 2021-05, Vol.22 (10), p.5160 |
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Sprache: | eng |
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Zusammenfassung: | Orexin A, an endogenous peptide involved in several functions including reward, acts via activation of orexin receptors OX
and OX
, Gq-coupled GPCRs. We examined the effect of a selective OX
agonist, OXA (17-33) on cytosolic calcium concentration, [Ca
]
, in neurons of nucleus accumbens, an important area in the reward circuit. OXA (17-33) increased [Ca
]
in a dose-dependent manner; the effect was prevented by SB-334867, a selective OX
receptors antagonist. In Ca
-free saline, the OXA (17-33)-induced increase in [Ca
]
was not affected by pretreatment with bafilomycin A1, an endo-lysosomal calcium disrupter, but was blocked by 2-APB and xestospongin C, antagonists of inositol-1,4,5-trisphosphate (IP
) receptors. Pretreatment with VU0155056, PLD inhibitor, or BD-1047 and NE-100, Sigma-1R antagonists, reduced the [Ca
]
response elicited by OXA (17-33). Cocaine potentiated the increase in [Ca
]
by OXA (17-33); the potentiation was abolished by Sigma-1R antagonists. Our results support an additional signaling mechanism for orexin A-OX
via choline-Sigma-1R and a critical role for Sigma-1R in the cocaine-orexin A interaction in nucleus accumbens neurons. |
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ISSN: | 1422-0067 1661-6596 1422-0067 |
DOI: | 10.3390/ijms22105160 |