About this item:

36 Views | 24 Downloads

Author Notes:


Tel.: +1-404-712-9538

Fax: +1-404-727-3425

Carried out experiments, F.M.; provided data and data analysis, G.C.; provided experimental support, E.L.R.; consulted on data analysis and manuscript preparation and editing, J.D.K.; consulted on protocol design and manuscript editing, J.M.S.; carried out experiments, data collection and analysis, wrote and finalized the manuscript, Y.W. All authors have read and agreed to the published version of the manuscript.

The authors declare no conflict of interest with the representation or interpretation of the reported research results.


Research Funding:

This work was supported by AHA Career Development Grant #18CDA34060053 to Y. Wang.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • adrenomedullin
  • water transport
  • cAMP
  • phospholipase C
  • protein kinase C
  • cGMP
  • CAMP
  • UREA

Adrenomedullin Inhibits Osmotic Water Permeability in Rat Inner Medullary Collecting Ducts


Journal Title:



Volume 9, Number 12


Type of Work:

Article | Final Publisher PDF


Adrenomedullin (ADM) is a vasodilator that causes natriuresis and diuresis. However, the direct effect of ADM on osmotic water permeability in the rat inner medullary collecting duct (IMCD) has not been tested. We investigated whether ADM and its ADM receptor components (CRLR, RAMP2, and 3) are expressed in rat inner medulla (IM) and whether ADM regulates osmotic water permeability in isolated perfused rat IMCDs. The mRNAs of ADM, CRLR, and RAMP2 and 3 were detected in rat IM. Abundant protein of CRLR and RAMP3 were also seen but RAMP2 protein level was extremely low. Adding ADM (100 nM) to the bath significantly decreased osmotic water permeability. ADM significantly decreased aquaporin-2 (AQP2) phosphorylation at Serine 256 (pS256) and increased it at Serine 261 (pS261). ADM significantly increased cAMP levels in IM. However, inhibition of cAMP by SQ22536 further decreased ADM-attenuated osmotic water permeability. Stimulation of cAMP by roflumilast increased ADM-attenuated osmotic water permeability. Previous studies show that ADM also stimulates phospholipase C (PLC) pathways including protein kinase C (PKC) and cGMP. We tested whether PLC pathways regulate ADM-attenuated osmotic water permeability. Blockade of either PLC by U73122 or PKC by rottlerin significantly augmented the ADM-attenuated osmotic water permeability and promoted pS256-AQP2 but did change pS261-AQP2. Inhibition of cGMP by L-NAME did not change AQP2 phosphorylation. In conclusion, ADM primarily binds to the CRLR-RAMP3 receptor to initiate signaling pathways in the IM. ADM reduced water reabsorption through a PLC-pathway involving PKC. ADM-attenuated water reabsorption may be related to decreased trafficking of AQP2 to the plasma membrane. cAMP is not involved in ADM-attenuated osmotic water permeability.

Copyright information:

© 2020 by the authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
Export to EndNote