Stimulation of catecholamine biosynthesis via the protein kinase C pathway by endothelin-1 in PC12 rat pheochromocytoma cells

Biochemical Pharmacology
K TakekoshiT Nakai

Abstract

It has been reported that endothelins (ETs) stimulate catecholamine release from chromaffin cells. However, it is not known whether ETs also affect catecholamine biosynthesis. Thus, using a rat pheochromocytoma cell line, PC12, we examined the effects of ETs on catecholamine biosynthesis. The mRNA level and activity of tyrosine hydroxylase (TH), a rate-limiting enzyme in catecholamine biosynthesis, were increased significantly by endothelin-1 (ET-1) (100nM). These stimulatory effects were inhibited completely by a blocker for the A-type endothelin receptor, BQ-123 [cyclo(D-alpha-aspartyl-L-prolyl-D-valyl-L-leucyl-D-tryptophyl)] (1 microM), but not by a blocker for the B-type endothelin receptor, BQ-788 (N-cis 2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine (1 microM). Also, Ro-32-0432 (3-[8-[(dimethylamino)methyl]-6,7,8,9-tetrahydropyrido-[1,2-a]indol-10-yl]-4-(1-methyl-3-indolyl)-H-pyrrole-2,5-dione hydrochloride) (100nM), a protein kinase C inhibitor, completely inhibited ET-1-induced increases in TH activity and mRNA level. Furthermore, ET-1 (100nM) significantly stimulated protein kinase C activity, as well as inositol 1,4,5-triphosphate production; these stimulatory effects ...Continue Reading

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Citations

Jan 21, 2011·Physiological Reviews·Donald E KohanDavid M Pollock
Aug 27, 2004·Neurosurgical Focus·Jason Heth
Mar 1, 2019·Scientific Reports·Héctor Carreño GutiérrezWilliam H J Norton
Feb 10, 2017·The Journal of Pharmacology and Experimental Therapeutics·Mohamed A Fouda, Abdel A Abdel-Rahman

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