Upregulation of vasopressin V1A receptor mRNA and protein in vascular smooth muscle cells following cyclosporin A treatment.

Détails

ID Serval
serval:BIB_65329ADDB8A9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Upregulation of vasopressin V1A receptor mRNA and protein in vascular smooth muscle cells following cyclosporin A treatment.
Périodique
British Journal of Pharmacology
Auteur(s)
Cottet-Maire F., Avdonin P.V., Roulet E., Buetler T.M., Mermod N., Ruegg U.T.
ISSN
0007-1188[print], 0007-1188[linking]
Statut éditorial
Publié
Date de publication
02/2001
Volume
132
Numéro
4
Pages
909-917
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
1. The major side effects of the immunosuppressive drug cyclosporin A (CsA) are hypertension and nephrotoxicity. It is likely that both are caused by local vasoconstriction. 2. We have shown previously that 20 h treatment of rat vascular smooth muscle cells (VSMC) with therapeutically relevant CsA concentrations increased the cellular response to [Arg8]vasopressin (AVP) by increasing about 2 fold the number of vasopressin receptors. 3. Displacement experiments using a specific antagonist of the vasopressin V1A receptor (V1AR) showed that the vasopressin binding sites present in VSMC were exclusively receptors of the V1A subtype. 4. Receptor internalization studies revealed that CsA (10(-6) M) did not significantly alter AVP receptor trafficking. 5. V1AR mRNA was increased by CsA, as measured by quantitative polymerase chain reaction. Time-course studies indicated that the increase in mRNA preceded cell surface expression of the receptor, as measured by hormone binding. 6. A direct effect of CsA on the V1AR promoter was investigated using VSMC transfected with a V1AR promoter-luciferase reporter construct. Surprisingly, CsA did not increase, but rather slightly reduced V1AR promoter activity. This effect was independent of the cyclophilin-calcineurin pathway. 7. Measurement of V1AR mRNA decay in the presence of the transcription inhibitor actinomycin D revealed that CsA increased the half-life of V1AR mRNA about 2 fold. 8. In conclusion, CsA increased the response of VSMC to AVP by upregulating V1AR expression through stabilization of its mRNA. This could be a key mechanism in enhanced vascular responsiveness induced by CsA, causing both hypertension and, via renal vasoconstriction, reduced glomerular filtration.
Mots-clé
Animals, Arginine Vasopressin/metabolism, Cells, Cultured, Cyclosporine/pharmacology, Heterogeneous-Nuclear Ribonucleoprotein D, Immunosuppressive Agents/pharmacology, Male, Muscle, Smooth, Vascular/cytology, Muscle, Smooth, Vascular/drug effects, RNA, Messenger/analysis, RNA-Binding Proteins/physiology, Rats, Rats, Inbred WKY, Receptors, Vasopressin/biosynthesis, Receptors, Vasopressin/drug effects, Up-Regulation
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 10:41
Dernière modification de la notice
20/08/2019 14:21
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