Verapamil decreases lymphocyte protein kinase C activity in humans.
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/microgram protein/min) tended to decrease after 1 week (3.50 +/- 0.20 pmol/micrograms protein/min) and was significantly decreased after 2 weeks (3.14 +/- 0.27 pmol/micrograms 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.
DePetrillo
P B
PB
Program in Clinical Pharmacology, Brown University School of Medicine, Providence, RI.
Abernethy
D R
DR
Wainer
I W
IW
Andrawis
N S
NS
D000328:Adult; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011493:Protein Kinase C / Q000097:blood / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D014700:Verapamil; D011493:Protein Kinase C