Endothelin-1 induces release of histamine and leukotriene C4 from mouse bone marrow-derived mast cells.
Whether specific binding sites for endothelin-1 and endothelin-3 exist in mouse bone marrow-derived mast cells (BMMC) and if these endothelins are capable of stimulating chemical mediator release from the cells was investigated. A single component of binding sites for endothelin-1 was found in the cells, but no binding sites for endothelin-3 were observed. Endothelin-1 at 1-100 nM concentration dependently induced release of histamine and immunoreactive leukotriene C4 from BMMC, while endothelin-3 at up to 100 nM did not stimulate the release of either mediator. Time course experiments revealed that the release of histamine and immunoreactive leukotriene C4 induced by endothelin-1 occurred rapidly, reaching near maximal levels within 20 s and 2 min, respectively, after the stimulation, while histamine release induced by antigen, at the concentration which induced an extent of release similar to that induced by 100 nM endothelin-1, required comparatively prolonged incubation (approximately 10 min for submaximal levels). Cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123), a selective antagonist of endothelin ETA receptors, not only dissociated [125I]endothelin-1 specifically bound to BMMC but also inhibited the release of both mediators from endothelin-1-induced cells. These results suggested strongly that BMMC have endothelin ETA receptors on their cell membrane, stimulation of which leads to chemical mediator release, probably via a mechanism different from that involved in the antigen-induced release.
Yamamura
H
H
Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
Nabe
T
T
Kohno
S
S
Ohata
K
K
D000818:Animals; D001665:Binding Sites; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D007116:Immunization, Passive; D017997:Leukotriene C4 / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010456:Peptides, Cyclic / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D017997:Leukotriene C4; D000001:Calcimycin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)