Adrenergic regulation of salt and fluid secretion in human medullary collecting duct cells

Am J Physiol Renal Physiol. 2004 Oct;287(4):F639-48. doi: 10.1152/ajprenal.00448.2003. Epub 2004 Jun 29.

Abstract

Transepithelial salt and fluid secretion mediated by cAMP in initial inner medullary collecting ducts (IMCDi) may be important for making final adjustments to urine composition. We examined in primary cultures of human IMCDi cells the effects of adrenergic receptor (AR) agonists and antagonists on intracellular cAMP levels, short-circuit current (I(SC)), and fluid secretion. Epinephrine (1 microM), norepinephrine (1 microM), and isoproterenol (10 nM) individually increased intracellular cAMP levels 57-, 2-, and 25-fold, respectively, and stimulated I(SC) 3.3-, 2.9-, and 3.4-fold, respectively. beta-AR activation increased net fluid secretion by cultured human IMCDi cell monolayers from 0.09 +/- 0.04 to 0.26 +/- 0.05 microl x h(-1) x cm(-2) and freshly isolated rat IMCDi from 0.02 +/- 0.01 to 0.09 +/- 0.02 nl x h(-1) x mm(-1). In monolayers, these effects were eliminated by blocking beta2-AR, but not beta1-AR. Activation of alpha2-AR with guanabenz inhibited isoproterenol-induced I(SC) by 37% in human IMCDi monolayers and fluid secretion by 91% in rat IMCDi. Immunohistochemistry of human medullary tissue sections revealed greater expression of beta2-AR than beta1-AR; beta2-AR was localized to the basolateral membranes of human IMCDi. Immunoblots identified alpha2A-AR and alpha2B-AR in cultured human IMCDi cell monolayers. We conclude that 1) catecholamines stimulate cAMP-dependent anion and fluid secretion by IMCDi cells primarily through beta2-AR activation and 2) alpha2-AR activation attenuates cAMP-dependent anion secretion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Anions / metabolism
  • Cells, Cultured
  • Chlorides / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Epinephrine / pharmacology*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Humans
  • Kidney Medulla / cytology
  • Kidney Medulla / metabolism
  • Kidney Tubules, Collecting / cytology*
  • Kidney Tubules, Collecting / drug effects
  • Kidney Tubules, Collecting / metabolism*
  • Norepinephrine / pharmacology
  • Rats
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Adrenergic, beta / metabolism
  • Salts / metabolism*
  • Sodium-Potassium-Chloride Symporters / metabolism
  • Solute Carrier Family 12, Member 2
  • Water-Electrolyte Balance / drug effects
  • Water-Electrolyte Balance / physiology*

Substances

  • Adrenergic alpha-Agonists
  • Anions
  • CFTR protein, human
  • Chlorides
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • SLC12A2 protein, human
  • Salts
  • Slc12a2 protein, rat
  • Sodium-Potassium-Chloride Symporters
  • Solute Carrier Family 12, Member 2
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Norepinephrine
  • Epinephrine