Ligand-dependent regulation of npr-a gene expression in inner medullary collecting duct cells. Cao, Li, Song Cang Chen, Tong Cheng, Michael H. Humphreys, and David G. Gardner. METABOLIC RESEARCH UNIT AND DEPARTMENT OF MEDICINE, UNIVERSITY OF CALIFORNIA AT SAN FRANCISCO
APStracts 5:0080F, 1998.
Atrial natriuretic peptide interacts with high affinity, guanylyl cyclase-linked receptors in the inner medullary collecting duct where it exerts important regulatory control over sodium handling. We sought to determine whether receptor activity in these cells would be modulated (down regulated) by prolonged exposure to ligand. A number of natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide and urodilatin) were found to decrease ligand -dependent natriuretic peptide receptor A (NPR-A) activity in inner medullary collecting duct cells. This inhibition was in direct proportion to their capacity to increase basal cGMP levels in this cell population. The reduction in receptor activity was accompanied by a dose- and time-dependent reduction in NPR-A mRNA levels in these cells. The decrease in transcript levels arose, in part, from a reduction in NPR-A gene transcription. Atrial natriuretic peptide reduced NPR-A gene promoter activity in a transiently transfected inner medullary collecting duct cell population. 8-bromo cGMP was also effective in inhibiting NPR-A mRNA levels and NPR-A promoter activity suggesting that the second messenger (i.e. cGMP) rather than ANP, itself, is responsible for down regulation of NPR-A gene expression. 

Received 15 December 1997; accepted in final form 26 March 1998.
APS Manuscript Number F395-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 24 April 1998