Downregulation of vasopressin [V.sub.2] receptor promoter activity via [V.sub.1a] receptor pathway

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Publisher: American Physiological Society
Document Type: Author abstract
Length: 219 words

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Abstract :

Vasopressin [V.sub.1a] and [V.sub.2] receptors ([V.sub.1a]R and [V.sub.2]R, respectively) distribute in the collecting duct of the kidney. Although the function of [V.sub.2]R mediating the antidiuretic effect of AVP has been investigated in detail, the role of [V.sub.1a]R in the collecting ducts has not been elucidated. In the present study, we have investigated the role of the [V.sub.1a]R pathway in [V.sub.2]R promoter activity. We cloned the 5'-flanking region of rat [V.sub.1a]R (r[V.sub.2]R) and investigated r[V.sub.2]R promoter activity in the LLC-P[K.sub.1] cell line transfected to express rat [V.sub.1a]R (r[V.sub.1a]R) dominantly (LLC-P[K.sub.1]/ r[V.sub.1a]R). AVP induced a transient increase, followed by a sustained decrease, of r[V.sub.2]R promoter activity in these cells. This AVP-induced decrease of r[V.sub.2]R promoter activity was inhibited by [V.sub.1a]R, but not [V.sub.2]R, antagonist. PMA mimicked this decrease of r[V.sub.2]R promoter activity. On the contrary, 8-(4-chlorophenylthio)-cAMP increased r[V.sub.2]R promoter activity. These PMA- and 8-(4-chlorophenylthio)-cAMP-induced effects were not observed on the deletion segment of the 5'-flanking region lacking CAAT and SP1 sites. In conclusion, 1) expression of the [V.sub.2]R is downregulated via the [V.sub.1a]R pathway in LLC-P[K.sub.1]/r[V.sub.1a]R cells, and 2) expression of the [V.sub.2]R is downregulated by the PMA-induced PKC pathway and upregulated by the cAMP-PKA pathway. These opposite effects of PKC and PKA appear to be regulated by the same promoter region of CAAT and SP1. transcription regulation; collecting ducts doi:10.1152/ajprenal.00358.2006

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Gale Document Number: GALE|A164253832