Premium
Verapamil decreases lymphocyte protein kinase C activity in humans
Author(s) -
Depetrillo Paolo B,
Abernethy Darrell R,
Wainer Irving W,
Andrawis Nabil S
Publication year - 1994
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1994.8
Subject(s) - verapamil , medicine , protein kinase a , endocrinology , pharmacology , lymphocyte , diltiazem , kinase , chemistry , calcium , biochemistry
To determine if clinically used doses of the calcium antagonist verapamil measurably alter intracellular transduction mechanisms associated with the phosphatidylinositol pathway, lymphocyte protein kinase C activity was determined in subjects in a drug‐free state, after 1 week of verapamil treatment (120 mg three times daily) and after a second week of verapamil treatment (240 mg sustained‐release preparation once daily). Nine healthy male volunteers were studied and in these subjects baseline protein kinase C activity (mean ± SEM; 5.07 ± 0.76 pmol/μg protein/min) tended to decrease after 1 week (3.50 ± 0.20 pmol/μg protein/min) and was significantly decreased after 2 weeks (3.14 ± 0.27 pmol/μg protein/min; p < 0.05 from baseline) of verapamil treatment. These data indicate that verapamil, at usual clinical doses, decreases protein kinase C activity in a marker tissue, the circulating lymphocyte. If protein kinase C activity in this tissue is a surrogate for other verapamil target tissues, such as vascular smooth muscle and heart muscle, these findings may provide insight into the in vivo mechanism by which verapamil decreases protein synthesis, limits cell growth, and reverses cellular hypertrophy in these tissues. Clinical Pharmacology and Therapeutics (1994) 55, 44–49; doi: 10.1038/clpt.1994.8