5-HT2 Receptor Regulation of Mitochondrial Genes: Unexpected Pharmacological Effects of Agonists and Antagonists

The Journal of Pharmacology and Experimental Therapeutics
Jennifer L HarmonRick G Schnellmann

Abstract

In acute organ injuries, mitochondria are often dysfunctional, and recent research has revealed that recovery of mitochondrial and renal functions is accelerated by induction of mitochondrial biogenesis (MB). We previously reported that the nonselective 5-HT2 receptor agonist DOI [1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine] induced MB in renal proximal tubular cells (RPTCs). The goal of this study was to determine the role of 5-HT2 receptors in the regulation of mitochondrial genes and oxidative metabolism in the kidney. The 5-HT2C receptor agonist CP-809,101 [2-[(3-chlorophenyl)methoxy]-6-(1-piperazinyl)pyrazine] and antagonist SB-242,084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] were used to examine the induction of renal mitochondrial genes and oxidative metabolism in RPTCs and in mouse kidneys in the presence and absence of the 5-HT2C receptor. Unexpectedly, both CP-809,101 and SB-242,084 increased RPTC respiration and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA expression in RPTCs at 1-10 nM. In addition, CP-809,101 and SB-242,084 increased mRNA expression of PGC-1α and the mitochondrial proteins NADH dehydrogenase ...Continue Reading

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Citations

May 31, 2018·American Journal of Physiology. Renal Physiology·Whitney S GibbsRick G Schnellmann
Aug 6, 2017·Journal of the American Society of Nephrology : JASN·Hazel H Szeto
Aug 28, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Sashaina E Fanibunda, Vidita A Vaidya
Oct 20, 2017·American Journal of Physiology. Renal Physiology·Whitney S GibbsRick G Schnellmann
May 11, 2019·Proceedings of the National Academy of Sciences of the United States of America·Sashaina E FanibundaVidita A Vaidya
Jul 20, 2019·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·L HolperJ J Mann
Jun 12, 2018·European Journal of Pharmacology·Manuella da L D BarrosLigia Galindo
Nov 25, 2021·Journal of Neurochemistry·Hannah N Saeger, David E Olson

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