Evidence that the antiproliferative effect of verapamil on afferent and efferent immune responses is independent of calcium channel inhibition.
Calcium channel blockers are capable of inhibiting the afferent and efferent limbs of the immune responses of human peripheral blood mononuclear cells in in vitro systems. This effect is thought to be related to the ability of the calcium channel blocker to limit the transmembrane flux of calcium. We report herein that two optical enantiomers of verapamil, one (S-) which is capable of blocking the slow calcium channel and mitogen-stimulated 45Ca++ uptake into human lymphocytes, while the other (R+) is incapable of either activity, share almost identical capabilities of depressing both the afferent and efferent limbs of immunity. These observations suggest that the inhibitory effects of verapamil on various afferent and efferent immune events are, in part at least, unrelated to the inhibition of transmembrane calcium flux.
Weir
M R
MR
Division of Nephrology, University of Maryland Hospital, Baltimore 21201.
Peppler
R
R
Gomolka
D
D
Handwerger
B S
BS
D000328:Adult; D000917:Antibody Formation / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D007519:Isoantigens / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007519:Isoantigens; D015375:Receptors, Interleukin-2; D014700:Verapamil