The in Vitro Effects of Histamine and Metiamide on Neutrophil Motility and Their Relationship to Intracellular Cyclic Nucleotide Levels

Abstract

Histamine at concentrations of 1 × 10^-5 M to 5 × 10^-5 M consistently increased neutrophil movement as measured in Boyden chambers. This effect was entirely caused by stimulation of chemokinesis (stimulated random migration) and true chemotaxis was inhibited by these concentrations. This inhibition of chemotaxis could be abolished by pretreatment with metiamide, an H-2 receptor antagonist, and levamisole, but not by diphenylhydramine, an H-1 receptor antagonist. Metiamide at similar concentrations produced a mild stimulation of chemokinesis but had no effect on true chemotaxis. The histamine effects on neutrophil motility were associated with increased levels of intracellular cAMP whereas cGMP levels were unaffected. Agents known to elevate intracellular cAMP levels produced effects on neutrophil motility similar to those of histamine. It is suggested that histamined exerts a 2-fold effect on neutrophil motility mediated via an H-2 receptor site and associated with elevated levels of cAMP.