Pharmacological and functional characterization of endothelin receptors in bovine trabecular meshwork and ciliary muscle.
To clarify the potential role of endothelin-1 (ET-1) in the pathogenesis of glaucoma, the endothelin receptors expressed in bovine trabecular meshwork (TM) and ciliary muscle (CM) were identified. TM and CM strips were subjected to ET-1 as well as to specific endothelin receptor antagonists. In both tissues BQ123, a specific ET-A receptor antagonist, substantially inhibited ET-1-induced contraction. BQ788, a specific ET-B receptor antagonist, showed only moderate effects. Both ET receptor types were detected in bovine TM and CM using Western blot analysis. ET-1 produced an increase in intracellular calcium in cultured TM cells. This effect was inhibited by BQ123, but not by BQ788. Thus, although both receptors are present, the ET-A receptor appears to play the predominant role in mediating contraction in both the TM and CM, while the ET-B receptor seems to contribute little to the overall ET-1 effect.
Institut für Klinische Physiologie, Charité, Universitätmedizin Berlin, Berlin, Deutschland.
Lars
L
Choritz
Rita
R
Rosenthal
Michael
M
Fromm
Michael H
MH
Foerster
Hagen
H
Thieme
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002924:Ciliary Body / Q000187:drug effects* / Q000378:metabolism; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000502:physiology*; D014129:Trabecular Meshwork / Q000187:drug effects / Q000378:metabolism
D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium