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.