Mechanism of histamine release by endothelin-1 distinct from that by antigen in mouse bone marrow-derived mast cells.
The mechanisms of endothelin-1-induced histamine release were examined and compared with those responsible for antigen-induced release by using passively sensitized mouse bone marrow-derived mast cells and various drugs that may influence histamine release. The following results were obtained: (1) Although islet-activating protein potently inhibited endothelin-1-induced histamine release, it did not affect the antigen-induced release. (2) Histamine release induced by endothelin-1 was relatively more sensitive to ethylenediaminetetraacetic acid than that induced by antigen, although extracellular Ca2+ is a requisite for both types of the release. (3) (8R*, 9S*, 11S*)-(-)-9- hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H, 11H-2, 7b,11a-triazadibenzo[a,g]cycloocta[c,d,e]trinden-1-one and (8R*, 9S*, 11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-14-n-propoxy-2,3,9,10-tet rahydro - 8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo[a,g]cycloocta-[c ,d,e] trinden-1-one, which possibly inhibit protein kinases, strongly inhibited antigen-induced histamine release, while these drugs alone did not inhibit endothelin-1-induced release. (4) Staurosporine, a non-selective protein kinase inhibitor, prevented the elevation of cytosolic Ca2+ concentrations induced by antigen, whereas that induced by endothelin-1 was not influenced; histamine release induced by either stimulus was greatly inhibited by the drug. These results indicate and/or suggest that some biological events induced by endothelin-1 leading to histamine release are different from those involved in the histamine release induced by antigen.
Yamamura
H
H
Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
Nabe
T
T
Kohno
S
S
Ohata
K
K
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D007116:Immunization, Passive; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011494:Protein Kinases; D019311:Staurosporine; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000470:Alkaloids; D000941:Antigens; D016232:Endothelins; D010566:Virulence Factors, Bordetella; D004492:Edetic Acid; D037342:Pertussis Toxin; D011494:Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium