Possible mechanisms of the concentration-dependent action of substance P to induce histamine release from rat peritoneal mast cells and the effect of extracellular calcium on mast-cell activation.
Rat peritoneal mast cells purified on a Percoll gradient were loaded with the fluorescent Ca2+ indicator fura-2 and were challenged with different concentrations of substance P (SP), and intracellular calcium concentrations ([Ca2+]i) were measured by a spectrofluorometric assay. SP at 5 x 10(-6) mol/l and 10(-5) mol/l caused a significant histamine release with a significant increase in [Ca2+]i in a dose-dependent manner. However, SP at 10(-8)-10(-6) mol/l did not induce either histamine release or increase in [Ca2+]i. Extracellular calcium at 0.9 mM inhibited the histamine release with a significant reduction of [Ca2+]i compared with that of the cells in a nominally calcium-free condition. These results indicate that the action of SP on rat mast cells relies upon [Ca2+]i to induce histamine release.
Amano
H
H
Department of Dermatology, Gunma University School of Medicine, Maebashi, Japan.
Kurosawa
M
M
Miyachi
Y
Y
D000818:Animals; D002118:Calcium / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D005110:Extracellular Space / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000276:immunology* / Q000494:pharmacology*
D013373:Substance P; D002118:Calcium