Effects of a novel antihypertensive drug, cilnidipine, on catecholamine secretion from differentiated PC12 cells

Hisayuki Uneyama, Hirohisa Uchida, Ryota Yoshimoto, Shinya Ueno, Kazuhide Inoue, Norio Akaike

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Effects of a novel dihydropyridine type of antihypertensive drug, cilnidipine, on the regulation of the catecholamine secretion closely linked to the intracellular Ca2+ were examined using nerve growth factor (NGF)- differentiated rat pheochromocytoma PC12 cells. By measuring catecholamine secretion with high-performance liquid chromatography coupled with an electrochemical detector, we showed that high K+ stimulation evoked dopamine release from PC12 cells both before and after NGF treatments. Cilnidipine depressed dopamine release both from NGF-treated and untreated PC12 cells in a concentration-dependent manner. In contrast, inhibition by nifedipine was markedly decreased in the differentiated PC12 cells. With intracellular Ca2+ concentration ([Ca2+](i)) measurements using fura 2, the elevation of high K+-evoked [Ca2+](i) was separated into nifedipine-sensitive and - resistant components. The nifedipine-resistant [Ca2+](i) increase was also blocked by cilnidipine, as well as ω-conotoxin-GVIA. By the use of the conventional whole-cell patch-clamp technique, the compositions of the high- voltage-activated Ca2+ channel currents in the NGF-treated PC12 cells were divided into types: L-type, N-type, and residual current components. It was also estimated that cilnidipine at 1 and 3 μmol/L strongly blocked the N- type current without affecting the residual current. These results suggest that cilnidipine inhibits catecholamine secretion from differentiated PC12 cells by blocking Ca2+ influx through the N-type Ca2+ channel, in addition to its well-known action on the L-type Ca2+ channel.

Original languageEnglish
Pages (from-to)1195-1199
Number of pages5
JournalHypertension
Volume31
Issue number5
DOIs
Publication statusPublished - May 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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