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• W4386046907 endingPage "627" @default.
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• W4386046907 abstract "Calcineurin is highly enriched in immune T cells and the nervous system. Calcineurin inhibitors, including cyclosporine and tacrolimus (FK506), are the cornerstone of immunosuppressive regimens for preserving transplanted organs and tissues. However, these drugs often cause persistent hypertension owing to excess sympathetic outflow, which is maintained by N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory input to the hypothalamic paraventricular nucleus (PVN). It is unclear how calcineurin inhibitors increase NMDAR activity in the PVN to augment sympathetic vasomotor activity. α2δ-1 (encoded by the Cacna2d1 gene), known colloquially as a calcium channel subunit, is a newly discovered NMDAR-interacting protein. In this study, we determined whether α2δ-1 plays a role in calcineurin inhibitor-induced synaptic NMDAR hyperactivity in the PVN and hypertension development.Immunoblotting and coimmunoprecipitation assays were used to quantify synaptic protein levels and the physical interaction between GluN1 (the obligatory NMDAR subunit) and α2δ-1. Whole-cell patch-clamp recordings of retrogradely labeled, spinally projecting PVN were conducted in perfused brain slices to measure presynaptic and postsynaptic NMDAR activity. Radio-telemetry was implanted in rodents to continuously record arterial blood pressure in conscious states.Prolonged treatment with FK506 in rats significantly increased protein levels of α2δ-1, GluN1, and the α2δ-1-GluN1 complex in PVN synaptosomes. These effects were blocked by inhibiting α2δ-1 with gabapentin or interrupting the α2δ-1-NMDAR interaction with an α2δ-1 C-terminus peptide. Treatment with FK506 potentiated the activity of presynaptic and postsynaptic NMDARs in spinally projecting PVN neurons; such effects were abolished by gabapentin, Cacna2d1 knockout, or α2δ-1 C-terminus peptide. Furthermore, microinjection of α2δ-1 C-terminus peptide into the PVN diminished renal sympathetic nerve discharges and arterial blood pressure that had been increased by FK506 treatment. Remarkably, concurrent administration of gabapentin prevented the development of FK506-induced hypertension in rats. Additionally, FK506 treatment induced sustained hypertension in wild-type mice but not in Cacna2d1 knockout mice.α2δ-1 is essential for calcineurin inhibitor-induced increases in synaptic NMDAR activity in PVN presympathetic neurons and sympathetic outflow. Thus, α2δ-1 and α2δ-1-bound NMDARs represent new targets for treating calcineurin inhibitor-induced hypertension. Gabapentinoids (gabapentin and pregabalin) could be repurposed for treating calcineurin inhibitor-induced neurogenic hypertension." @default.
• W4386046907 created "2023-08-23" @default.
• W4386046907 creator A5000743652 @default.
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• W4386046907 date "2023-09-15" @default.
• W4386046907 modified "2023-10-17" @default.
• W4386046907 title "Brain α2δ-1–Bound NMDA Receptors Drive Calcineurin Inhibitor–Induced Hypertension" @default.
• W4386046907 cites W1931139744 @default.
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• W4386046907 cites W1970581037 @default.
• W4386046907 cites W1983318444 @default.
• W4386046907 cites W1985246817 @default.
• W4386046907 cites W1993519091 @default.
• W4386046907 cites W1993832663 @default.
• W4386046907 cites W1997271863 @default.
• W4386046907 cites W2007942013 @default.
• W4386046907 cites W2008348302 @default.
• W4386046907 cites W2009353202 @default.
• W4386046907 cites W2014413823 @default.
• W4386046907 cites W2019904042 @default.
• W4386046907 cites W2022145302 @default.
• W4386046907 cites W2026388670 @default.
• W4386046907 cites W2027171843 @default.
• W4386046907 cites W2030202502 @default.
• W4386046907 cites W2037870956 @default.
• W4386046907 cites W2045346149 @default.
• W4386046907 cites W2052655550 @default.
• W4386046907 cites W2059401878 @default.
• W4386046907 cites W2066519829 @default.
• W4386046907 cites W2075025454 @default.
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• W4386046907 cites W2079311079 @default.
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• W4386046907 cites W2086824640 @default.
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• W4386046907 cites W2095522679 @default.
• W4386046907 cites W2103289578 @default.
• W4386046907 cites W2107104194 @default.
• W4386046907 cites W2107721698 @default.
• W4386046907 cites W2111841009 @default.
• W4386046907 cites W2124609197 @default.
• W4386046907 cites W2127507515 @default.
• W4386046907 cites W2127677921 @default.
• W4386046907 cites W2131958615 @default.
• W4386046907 cites W2132208680 @default.
• W4386046907 cites W2136964355 @default.
• W4386046907 cites W2168840998 @default.
• W4386046907 cites W2171172510 @default.
• W4386046907 cites W21837210 @default.
• W4386046907 cites W2214491343 @default.
• W4386046907 cites W2238399847 @default.
• W4386046907 cites W2256689525 @default.
• W4386046907 cites W2270314129 @default.
• W4386046907 cites W2333207361 @default.
• W4386046907 cites W2339063247 @default.
• W4386046907 cites W2542590893 @default.
• W4386046907 cites W2743574546 @default.
• W4386046907 cites W2761859218 @default.
• W4386046907 cites W2793983403 @default.
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• W4386046907 doi "https://doi.org/10.1161/circresaha.123.322562" @default.
• W4386046907 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37605933" @default.
• W4386046907 hasPublicationYear "2023" @default.
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