Divergent action of calcium channel blockers on ATP-binding cassette protein expression

Kazuhiro Hasegawa, Shu Wakino, Takeshi Kanda, Kyoko Yoshioka, Satoru Tatematsu, Koichiro Honma, Ichiro Takamatsu, Naoki Sugano, Koichi Hayashi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Calcium channel blockers (CCBs) are widely used in clinical practice, and have been reported to be effective in preventing the progression of atherosclerosis. We examined whether various types of calcium channel blockers affected the expression of ATP binding cassette transporter A1 (ABCA1), a factor contributing to anti-atherogenesis. Undifferentiated monocytic cell line, THP-1 cells were maintained in RPMI 1640 medium and treated with different kinds of calcium channel blockers. Among the calcium channel blockers tested, aranidipine and efonidipine increased ABCA1 protein expression without an increase in ABCA1 mRNA expression, whereas other calcium channel blockers (eg, nifedipine, amlodipine, and nicardipine) or T-type calcium channel blockers (eg, mibefradil and nickel chloride) failed to upregulate ABCA1 expression. H89, a protein kinase A inhibitor inhibited the aranidipine-induced ABCA1 protein expression, whereas genistein (a tyrosine kinase inhibitor), or AG490 (a JAK-2 inhibitor) had no effects. Neither of these inhibitors suppressed the efonidipine-induced ABCA1 protein expression. Intracellular cAMP levels were elevated only by aranidipine, but not by efonidipine. In conclusion, aranidipine and efonidipine have the ability to induce ABCA1 protein by distinct mechanisms; protein kinase A is involved in the aranidipine-induced ABCA1 upregulation. This non-class effect of calcium channel blockers may potentially offer beneficial action in the treatment of hypertensive subjects with atherosclerosis.

Original languageEnglish
Pages (from-to)787-793
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume46
Issue number6
DOIs
Publication statusPublished - 2005 Dec

Fingerprint

ATP-Binding Cassette Transporters
Calcium Channel Blockers
Carrier Proteins
Adenosine Triphosphate
Atherosclerosis
Cyclic AMP-Dependent Protein Kinases
Proteins
Up-Regulation
Mibefradil
T-Type Calcium Channels
Nicardipine
Amlodipine
Genistein
Nifedipine
Protein Kinase Inhibitors
Protein-Tyrosine Kinases
aranidipine
Cell Line
Messenger RNA
efonidipine

Keywords

  • ABCA1
  • Aranidipine
  • Calcium channel blocker
  • cAMP
  • Efonidipine
  • Protein kinase A

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Divergent action of calcium channel blockers on ATP-binding cassette protein expression. / Hasegawa, Kazuhiro; Wakino, Shu; Kanda, Takeshi; Yoshioka, Kyoko; Tatematsu, Satoru; Honma, Koichiro; Takamatsu, Ichiro; Sugano, Naoki; Hayashi, Koichi.

In: Journal of Cardiovascular Pharmacology, Vol. 46, No. 6, 12.2005, p. 787-793.

Research output: Contribution to journalArticle

Hasegawa, Kazuhiro ; Wakino, Shu ; Kanda, Takeshi ; Yoshioka, Kyoko ; Tatematsu, Satoru ; Honma, Koichiro ; Takamatsu, Ichiro ; Sugano, Naoki ; Hayashi, Koichi. / Divergent action of calcium channel blockers on ATP-binding cassette protein expression. In: Journal of Cardiovascular Pharmacology. 2005 ; Vol. 46, No. 6. pp. 787-793.
@article{50c9b9a24d8540c2928b6728c5884324,
title = "Divergent action of calcium channel blockers on ATP-binding cassette protein expression",
abstract = "Calcium channel blockers (CCBs) are widely used in clinical practice, and have been reported to be effective in preventing the progression of atherosclerosis. We examined whether various types of calcium channel blockers affected the expression of ATP binding cassette transporter A1 (ABCA1), a factor contributing to anti-atherogenesis. Undifferentiated monocytic cell line, THP-1 cells were maintained in RPMI 1640 medium and treated with different kinds of calcium channel blockers. Among the calcium channel blockers tested, aranidipine and efonidipine increased ABCA1 protein expression without an increase in ABCA1 mRNA expression, whereas other calcium channel blockers (eg, nifedipine, amlodipine, and nicardipine) or T-type calcium channel blockers (eg, mibefradil and nickel chloride) failed to upregulate ABCA1 expression. H89, a protein kinase A inhibitor inhibited the aranidipine-induced ABCA1 protein expression, whereas genistein (a tyrosine kinase inhibitor), or AG490 (a JAK-2 inhibitor) had no effects. Neither of these inhibitors suppressed the efonidipine-induced ABCA1 protein expression. Intracellular cAMP levels were elevated only by aranidipine, but not by efonidipine. In conclusion, aranidipine and efonidipine have the ability to induce ABCA1 protein by distinct mechanisms; protein kinase A is involved in the aranidipine-induced ABCA1 upregulation. This non-class effect of calcium channel blockers may potentially offer beneficial action in the treatment of hypertensive subjects with atherosclerosis.",
keywords = "ABCA1, Aranidipine, Calcium channel blocker, cAMP, Efonidipine, Protein kinase A",
author = "Kazuhiro Hasegawa and Shu Wakino and Takeshi Kanda and Kyoko Yoshioka and Satoru Tatematsu and Koichiro Honma and Ichiro Takamatsu and Naoki Sugano and Koichi Hayashi",
year = "2005",
month = "12",
doi = "10.1097/01.fjc.0000187976.60262.bf",
language = "English",
volume = "46",
pages = "787--793",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Divergent action of calcium channel blockers on ATP-binding cassette protein expression

AU - Hasegawa, Kazuhiro

AU - Wakino, Shu

AU - Kanda, Takeshi

AU - Yoshioka, Kyoko

AU - Tatematsu, Satoru

AU - Honma, Koichiro

AU - Takamatsu, Ichiro

AU - Sugano, Naoki

AU - Hayashi, Koichi

PY - 2005/12

Y1 - 2005/12

N2 - Calcium channel blockers (CCBs) are widely used in clinical practice, and have been reported to be effective in preventing the progression of atherosclerosis. We examined whether various types of calcium channel blockers affected the expression of ATP binding cassette transporter A1 (ABCA1), a factor contributing to anti-atherogenesis. Undifferentiated monocytic cell line, THP-1 cells were maintained in RPMI 1640 medium and treated with different kinds of calcium channel blockers. Among the calcium channel blockers tested, aranidipine and efonidipine increased ABCA1 protein expression without an increase in ABCA1 mRNA expression, whereas other calcium channel blockers (eg, nifedipine, amlodipine, and nicardipine) or T-type calcium channel blockers (eg, mibefradil and nickel chloride) failed to upregulate ABCA1 expression. H89, a protein kinase A inhibitor inhibited the aranidipine-induced ABCA1 protein expression, whereas genistein (a tyrosine kinase inhibitor), or AG490 (a JAK-2 inhibitor) had no effects. Neither of these inhibitors suppressed the efonidipine-induced ABCA1 protein expression. Intracellular cAMP levels were elevated only by aranidipine, but not by efonidipine. In conclusion, aranidipine and efonidipine have the ability to induce ABCA1 protein by distinct mechanisms; protein kinase A is involved in the aranidipine-induced ABCA1 upregulation. This non-class effect of calcium channel blockers may potentially offer beneficial action in the treatment of hypertensive subjects with atherosclerosis.

AB - Calcium channel blockers (CCBs) are widely used in clinical practice, and have been reported to be effective in preventing the progression of atherosclerosis. We examined whether various types of calcium channel blockers affected the expression of ATP binding cassette transporter A1 (ABCA1), a factor contributing to anti-atherogenesis. Undifferentiated monocytic cell line, THP-1 cells were maintained in RPMI 1640 medium and treated with different kinds of calcium channel blockers. Among the calcium channel blockers tested, aranidipine and efonidipine increased ABCA1 protein expression without an increase in ABCA1 mRNA expression, whereas other calcium channel blockers (eg, nifedipine, amlodipine, and nicardipine) or T-type calcium channel blockers (eg, mibefradil and nickel chloride) failed to upregulate ABCA1 expression. H89, a protein kinase A inhibitor inhibited the aranidipine-induced ABCA1 protein expression, whereas genistein (a tyrosine kinase inhibitor), or AG490 (a JAK-2 inhibitor) had no effects. Neither of these inhibitors suppressed the efonidipine-induced ABCA1 protein expression. Intracellular cAMP levels were elevated only by aranidipine, but not by efonidipine. In conclusion, aranidipine and efonidipine have the ability to induce ABCA1 protein by distinct mechanisms; protein kinase A is involved in the aranidipine-induced ABCA1 upregulation. This non-class effect of calcium channel blockers may potentially offer beneficial action in the treatment of hypertensive subjects with atherosclerosis.

KW - ABCA1

KW - Aranidipine

KW - Calcium channel blocker

KW - cAMP

KW - Efonidipine

KW - Protein kinase A

UR - http://www.scopus.com/inward/record.url?scp=33644687864&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644687864&partnerID=8YFLogxK

U2 - 10.1097/01.fjc.0000187976.60262.bf

DO - 10.1097/01.fjc.0000187976.60262.bf

M3 - Article

VL - 46

SP - 787

EP - 793

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 6

ER -