Dihydropyridine Ca2+ channel antagonists inhibit the salvage pathway for DNA synthesis in human vascular smooth muscle cells

Agrotis, A, Little, PJ, Saltis, J and Bobik, A (1993) Dihydropyridine Ca2+ channel antagonists inhibit the salvage pathway for DNA synthesis in human vascular smooth muscle cells. European Journal of Pharmacology: Molecular Pharmacology, 244 3: 269-275. doi:10.1016/0922-4106(93)90152-Y


Author Agrotis, A
Little, PJ
Saltis, J
Bobik, A
Title Dihydropyridine Ca2+ channel antagonists inhibit the salvage pathway for DNA synthesis in human vascular smooth muscle cells
Journal name European Journal of Pharmacology: Molecular Pharmacology
ISSN 0922-4106
Publication date 1993-02-15
Sub-type Article (original research)
DOI 10.1016/0922-4106(93)90152-Y
Volume 244
Issue 3
Start page 269
End page 275
Total pages 7
Language eng
Subject 3004 Pharmacology
2804 Cellular and Molecular Neuroscience
Abstract We examined the mechanisms by which Ca2+ channel antagonists inhibit the growth of smooth muscle cells by determining their effect on epidermal growth factor (EGF)-stimulated (i) induction of the early signalling gene, c-fos, (ii) incorporation of [3H]thymidine into cells as a measure of DNA synthesis, and (iii) increase in cell number. Verapamil, diltiazem, and the dihydropyridines felodipine, MDL 72892 A-15 (MDL) and nisoldipine had no effect on EGF-stimulated c-fos mRNA induction. Furthermore, only small inhibitory effects were observed on EGF-stimulated increases in cell number; felodipine, MDL, and nisoldipine at 0.3 μM inhibited EGF-stimulated cell proliferation by 9, 11, and 15%, respectively. In contrast, the dihydropyridine Ca2+ channel antagonists were found to be potent inhibitors of [3H]thymidine incorporation suggesting that they inhibit DNA synthesis. However, further examination revealed that the potent effects of dihydropyridine Ca2+ channel antagonists on [3H]thymidine incorporation were due not to an effect on incorporation of [3H]thymidine into DNA, but to a marked inhibitory effect on the cellular uptake of [3H]thymidine. Thus, we conclude that the small antiproliferative effects of the dihydropyridine antagonists are predominantly due to their ability to inhibit the activity of the salvage pathway for thymidylate synthesis in human vascular smooth muscle cells.
Keyword Ca2+ channel antagonists
Proliferation
Smooth muscle (vascular)
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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