Upregulation of V1a vasopressin receptors by glucocorticoids.
WRK1 cells (a rat mammary tumor cell line) exhibit a vasopressinergic receptor of V1a subtype tightly coupled to phospholipase C. Addition of dexamethasone to the culture medium principally potentiated the vasopressin-sensitive accumulation of inositol phosphates and to a lesser extent the NaF-sensitive phospholipase C activity. On the opposite, such treatment was without effect on the basal level of intracellular inositol phosphates or on bradykinin- or serotonin-sensitive phosphoinositide metabolisms. Glucocorticoid receptors were probably involved in these actions since dexamethasone was found to be more potent than aldosterone or corticosterone. Dexamethasone treatment also increased the number of vasopressin binding sites without affecting its affinity for vasopressin or other specific vasopressin analogues. These results strongly suggest that dexamethasone principally acts at the vasopressin receptor level by affecting its synthesis and/or the translation of its mRNA and also affects the G protein that couples the V1a receptor to the phospholipase C. These results explain how glucocorticoids may regulate the transduction mechanisms involved in vasopressin actions on WRK1 cells. They provide explanations for understanding the cross talk between adrenal steroids and hormones, which mobilize intracellular calcium.
Colson
P
P
Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale de Pharmacologie-Endocrinologie, Montpellier, France.
Ibarondo
J
J
Devilliers
G
G
Balestre
M N
MN
Duvoid
A
A
Guillon
G
G
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D051381:Rats; D017483:Receptors, Vasopressin / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000648:ultrastructure; D010738:Type C Phospholipases / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D007295:Inositol Phosphates; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D003907:Dexamethasone; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins