Atrial natriuretic peptide inhibits the production and secretion of endothelin from cultured endothelial cells. Mediation through the C receptor.

Abstract

Atrial natriuretic peptide (ANP) and endothelin-1 (ET-1) are vasoactive peptides produced in cells of the cardiovascular system. We examined the effects of ANP on ET-1 transcription, production (translation), and secretion in cultured bovine aortic endothelial cells (BAEC). ANP and C-ANP 4-23 (a specific ligand for the C or non-guanylate cyclase receptor) equipotently inhibited the synthesis of prepro-ET-1 and ET-1 proteins in BAEC by at least 50%. Both of these forms of ANP and another C receptor specific ligand, nanopiperazine ANP (11-15)-NH2, inhibited ET-1 secretion by as much as 55%. LY 83583, an inhibitor of ANP-induced cGMP generation, failed to reverse the ANP-induced inhibition of ET-1 secretion. This further indicated that the guanylate cyclase-linked B receptor is not involved. The decreased ET-1 secretion caused by C-ANP 4-23 was reversed by 8-bromo-cAMP or amiloride, which prevents ANP-induced inhibition of cAMP. We also found that ANP and C-ANP 4-23 augmented ET-1 mRNA levels in BAEC by prolonging the mRNA half-life. ANP or cycloheximide comparably inhibited ET-1 translation while increasing ET-1 mRNA levels, suggesting that the two events are related. These results indicate that ANP inhibits ET-1 protein production and secretion while stabilizing the ET-1 mRNA. The effects of ANP are mediated through the C receptor and are probably the result of ANP inhibiting the generation of cAMP. These findings suggest a potentially important new function for this receptor to mediate, in part, the interactions of ANP and ET in the vasculature.

Statistics

050100150'95'97'99'01'03'05'07'09'11'13'15'17
Citations per Year

596 Citations

Semantic Scholar estimates that this publication has 596 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Hu1992AtrialNP, title={Atrial natriuretic peptide inhibits the production and secretion of endothelin from cultured endothelial cells. Mediation through the C receptor.}, author={Ren-ming Hu and Ellis Robert Levin and Ali Pedram and Holly J. Frank}, journal={The Journal of biological chemistry}, year={1992}, volume={267 24}, pages={17384-9} }