STUDIES ON THE MECHANISMS OF THE INHIBITORY EFFECT OF N-5' ON HISTAMINE RELEASE FROM RAT PERITONEAL EXUDATE CELLS

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To investigate the mechanisms for the inhibition of IgE-mediated histamine release from rat peritoneal exudate cells (PEC) by N-5', we studied the relation between the inhibitory effect of N-5' on histamine release and the intracellular levels of adenine nucleotides such as ATP and cAMP. Evident histamine release was induced by the addition of specific antigen to rat PEC sensitized with IgE antiserum in vitro, and the release showed a maximum 30 sec after the antigen challenge. In the same time course as the histamine release, the intracellular levels of ATP and cAMP decreased. N-5' significantly inhibited the histamine release and a decrease in ATP level as a result of the antigen-antibody reaction. A decrease in cAMP level showed a tendency to be sup pressed by N-5'. Antigen-induced ¹⁴CO₂ production for 6-¹⁴C-glucose in the sensitized PEC was 3 times that seen in the case without antigen. N-5' dramatically suppressed the accerelation in the production of ¹⁴CO₂. Differing from the action of papaverine, the inhibitory effect of N-5' on the IgE-mediated histamine release from rat PEC was identical both in the presence or in the absence of glucose. N-5' scarcely affected the ATP level in the non-sensitized PEC in the glucose-free medium. On the other hand, N-5' inhibited the activity of Na⁺, K⁺-ATPase, one of the ATP-consuming enzymes, in a dose dependent fashion. From these results, it is presumed that the suppression of ATP utilization through the inhibition of Na⁺, K⁺-ATPase activity is involved in the inhibition of histamine release by N-5'. The relation between the inhibitory effect of N-5' on histamine release and both nucleotides was also discussed.