CALCIUM-CHANNEL BLOCKERS ENHANCE THE INHIBITORY-ACTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON THE LUMINOL-DEPENDENT CHEMILUMINESCENCE - DIFFERENTIAL-EFFECTS OF TENOXICAM

Indomethacin (0.15-5 mu g/ml), diclofenac (0.1-1.0 mu g/ml) and tenoxi cam (1.25-50 mu g/ml) or the calcium channel blockers, verapamil (25-4 00 mu g/ml) and diltiazem (25-300 mu g/ml), when added separately, inh ibited the chemiluminescence (CL) response of isolated human polymorph onuclear leukocytes (PMNs) stimulated with either the soluble agent, p horbol myristate acetate (PMA) or by particulate opsonized zymosan (OP Z) in a concentration-dependent manner. When diltiazem was combined wi th either indomethacin or diclofenac, in vitro, the inhibitory effect on PMA or OPZ-induced CL response was synergistic. Similarly, verapami l produced such a synergistic effect on CL when added together with in domethacin or diclofenac. In contrast, tenoxicam failed to show any sy nergistic effect on the CL response when it was combined with either d iltiazem or verapamil. The NSAIDs and the calcium channel blockers did not significantly affect the viability of PMNs and their inhibitory e ffects on CL were readily reversible when PMNs were washed with phosph ate buffered saline (PBS). II is concluded that extracellular calcium may be essential for indomethacin and diclofenac but not tenoxicam to increase the inhibitory effects of NSAIDs on the CL response.