NDLI: Transcriptional down-regulation of the rabbit pulmonary artery endothelin B receptor during phenotypic modulation

Content Provider	PubMed Central
Author	Owe-young, R. Schyvens, C. G. Qasabian, R. A. Conigrave, A. D. Macdonald, P. S. Williamson, D. J.
Copyright Year	1999
Abstract	We confirmed that endothelium-independent contraction of the rabbit pulmonary artery (RPA) is mediated through both an endothelin A (ETAR) and endothelin B (ETB2R) receptor. The response of endothelium-denuded RPA rings to endothelin-1 (ET-1, pD2=7.84±0.03) was only partially inhibited by BQ123 (10 μM), an ETAR antagonist. Pretreatment with 1 nM sarafotoxin S6c (S6c), an ETBR agonist, desensitized the ETB2R and significantly attenuated the response to ET-3 (pD2=7.40±0.02 before, <6.50 after S6c). Pretreatment with S6c had little effect on the response to ET-1, but BQ123 (10 μM) caused a parallel shift to the right of the residual ETAR-mediated response to ET-1 (pD2=7.84±0.03 before S6c, 7.93±0.03 after S6c, 6.81±0.05 after BQ123). Binding of radiolabelled ET-1 to early passage cultures of RPA vascular smooth muscle cells (VSMC) displayed two patterns of competitive displacement characteristic of the ETAR (BQ123 pIC50=8.73±0.05) or ETB2R (S6c pIC50=10.15). Competitive displacement experiments using membranes from late passage VSMC confirmed only the presence of the ETAR (ET-1 pIC50=9.3, BQ123 pIC50=8.0, S6c pIC50<6.0). The ETAR was functionally active and coupled to rises in intracellular calcium which exhibited prolonged homologous desensitization. Using a reverse transcriptase polymerase chain reaction for the rabbit ETB2R, we demonstrated the absence of mRNA expression in phenotypically modified VSMC. We conclude that the ETB2R expressed by VSMC which mediates contraction of RPA is rapidly down-regulated at the transcriptional level during phenotypic modulation in vitro.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0702280
Ending Page	110
Page Count	8
Starting Page	103
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	1
Volume Number	126
Language	English
Publisher Date	1999-01-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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