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A Mechanism for Inhibitory Effects of Diverse Compounds on in vitro Antigenic Lymphocyte Stimulation and Histamine Release From Leukocytes

Ethanol (E), nicotinamide (N), cyclic 3′, 5′ adenosine monophosphate (AMP) and theophylline (T) are examples of dissimilar compounds found to inhibit the fundamental cellular responses of antigenic histamine release and lymphocyte stimulation. As glucose is a prime source of energy and intermediates essential to cellular responses, the effects of the compounds on glucose utilization by leukocytes were determined, and corresponding inhibition of glucose metabolism was revealed. The molar concentrations required for comparable degrees of inhibition were closely similar for the two cellular responses and glucose utilization. To ascertain loci of inhibitory actions, the effects on conversion of glucose labeled with 14CO at various sites to 14CO2 were compared in suspensions of intact leukocytes and extracts of leukocytes devoid of cell membrance or nuclei. E and N were inhibitory mainly with intact cells and appear to affect glucose transport across the cell membrane. AMP and T also inhibited conversion by cell-free extracts and thus enzyme systems within the cell. Inhibition of glucose utilization by leukocytes is a common property of inhibitors of cellular responses, including E, N, Amp, T, and we found likewise for cortisol, colchicine, and chloroquine. The loci of action of the diverse compounds in the complex steps in utilization of glucose by leukocytes differ.The in vitro systems employed to compare cellular responses with glucose utilization are useful in fundamental studies and also convenient for screening of compounds for activity in these processes.