Pb. Depetrillo et al., VERAPAMIL DECREASES LYMPHOCYTE PROTEIN-KINASE-C ACTIVITY IN HUMANS, Clinical pharmacology and therapeutics, 55(1), 1994, pp. 44-49
To determine if clinically used doses of the calcium antagonist verapa
mil measurably alter intracellular transduction mechanisms associated
with the phosphatidylinositol pathway, lymphocyte protein kinase C act
ivity was determined in subjects in a drug-free state, after 1 week of
verapamil treatment (120 mg three times daily) and after a second wee
k of verapamil treatment (240 mg sustained-release preparation once da
ily). Nine healthy male volunteers were studied and in these subjects
baseline protein kinase C activity (mean +/- SEM; 5.07 +/- 0.76 pmol/m
u g protein/min) tended to decrease after 1 week (3.50 +/- 0.20 pmol/m
u g protein/min) and was significantly decreased after 2 weeks (3.14 /- 0.27 pmol/mu g protein/ min; p < 0.05 from baseline) of verapamil t
reatment. These data indicate that verapamil, at usual clinical doses,
decreases protein kinase C activity in a marker tissue, the circulati
ng lymphocyte. If protein kinase C activity in this tissue is a surrog
ate 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.