K-channel blocking drugs induce histamine release and 45Ca uptake in isolated mast cells.
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.
Department of Physiology and Pharmacology, University of Salamanca, Spain.
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Eleno
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Botana
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Espinosa
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006636:Histamine Release; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013034:Sparteine / Q000494:pharmacology
D015221:Potassium Channels; D013034:Sparteine; D011803:Quinine; D015761:4-Aminopyridine; D002118:Calcium