K-Channel Blocking Drugs Induce Histamine Release and ⁴⁵Ca Uptake in Isolated Mast Cells

Abstract

Histamine secretion and ⁴⁵Ca uptake processes were studied in mast cells treated with four K⁺ channel blocking drugs in physiological saline and in media containing different ionic concentrations. Quinine, 4-aminopyridine and sparteine were effective as histamine-releasing agents when mast cells were incubated in physiologic saline solution. The dose-response profile obtained was in the range of 0.1–0.5 mM for quinine, 1–10 for 4-aminopyridine and 0.5–5 mM for sparteine and did not show significant differences between purified and unpurified mast cells. By contrast, tetraethylammonium (1–100 mM) did not induce histamine release. The presence of high K⁺ or Rb⁺ concentrations in the medium (Tris-K⁺ or Tris-Rb⁺, both at 150 mM) displaced the profile obtained to the right in cells stimulated with 4-aminopyridine or sparteine, but abolished histamine release induced by quinine. Additionally, all three K⁺ channel blockers increased ⁴⁵Ca uptake in mast cells. The exact mechanism of the action of K⁺ channel blockers on mast cells is unknown. However, the fact that the drugs used were effective as histamine-releasing and ⁴⁵Ca uptake promoters suggests both that mast cells might be endowed with a K⁺ channel activity and that the blockade of this should open certain calcium channels, leading to elevated intracellular Ca²⁺ levels which in turn activate mast cell secretion.

Comparison of Salicylate- and Quinine-Induced Tinnitus in Rats

“…Although the clinical manifestations of quinine and salicylate on tinnitus induction are similar, different mechanisms of ototoxicity may be present. Many of quinine’s effects have been reported to induce tinnitus; these include vasoconstriction in the cochlea through an alteration of the cochlear blood flow and the interaction with calcium channels and calcium-dependent potassium channels (17-19). …”

Amiloride‐dependent transport is the main mechanism implicated in sodium iinflux regulation in rat mast cells

“…There are few data describing the movements of sodium across the plasma membrane of mast cells and the coupled regulation of intracellular pH to sodium by the Na+/H+ pump (Botana et al, 19921, although the membrane permeability to other ions has been recognized as an important element of the signal transduction process (Bronner et al, 1991, Eleno et al 1990). Some functional studies carried out by Beauvais et al (1992) show that in human basophils external sodium is inhibitory to histamine release.…”

Effect of ion composition on the changes in membrane potential induced with several stimuli in rat mast cells

“…But the effect of this compound is linked to an increase in external calcium influx when this cation is present. This influx is probably related to a membrane potential change (Eleno et al, 1990;Hoth and Penner, 1992). Therefore, we studied the effect of calcium movements on membrane potential with thapsigargin and ionophore A23187.…”