The adenylate cyclase coupled vasopressin receptor activates the
aquaporin-2 promoter via a dual effect on cre and ap1 elements.
Yasui, Masato, Sergey M. Zelenin, Gianni Celsi, and Anita Aperia.
Department of Woman and Child Health, Pediatric Unit, St.
G[diaeresis]oran's Children's Hospital, Karolinska Institute, S-112
81, Stockholm, Sweden, Novosibirsk Institute of Bioorganic Chemistry,
630090, Novosibirsk, Russia
APStracts 3:0226F, 1996.
Vasopressin plays an essential role for the regulation of water
balance by activating the collecting duct specific water channel,
aquaporin 2 (AQP2). Here we present evidence that vasopressin may
also act as a long-term, transcriptional regulator of AQP2. The
studies were performed in LLC-PK1 cells, which normally express V2
receptor (V2R), and which were transfected with a fragment of the
human AQP2 promoter. Activation of the adenylate cyclase coupled V2R
in LLC-PK1 cells induced phosphorylation of cAMP-responsive element
-binding protein (CREB) and expression of c-Fos. Binding of these
factors to the CRE and AP1 site did, in combination, lead to AQP2
promoter activation. These results establish the role of vasopressin
as a regulator of transcription and are the first example of how a
message from a highly specific receptor is, via a dual effect of the
cAMP signal on CREB and immediate early gene expression, transduced
to the transcription of a final target protein with known biological
effects.
Received 12 July 1996; accepted in final form 12 December 1996.
APS Manuscript Number F197-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996