A2 adenosine receptors in Mongolian gerbil middle ear epithelium and their regulation of Cl- secretion

M. Furukawa, K. Ikeda, T. Oshima, H. Suzuki, M. Yamaya, H. Sasaki, T. Takasaka

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Abstract

The present study investigates the effects of adenosine and its analogues on Cl- secretion in primary cultures of gerbil middle ear epithelium. Short-circuit current (I(sc)), an index of transepithelial active transport, was measured on the same cells cultured on porous filters. Baseline I(sc) and transepithelial resistance were 27.0 ± 0.7 μA cm-2 and 275 ± 7 Ω cm2, respectively (n = 178). Extracellular adenosine and its analogues elicited a sustained increase in I(sc) when added to apical or basolateral surfaces. Both the A(2A) selective agonist 2-p-(2- carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine and the A(2A)/A(2B) nonselective agonist 5'-(N-ethyl-carboxamido)adenosine (NECA) increased I(sc), but NECA was more effective than CGS21680. A1 selective antagonist 8-cyclopentyl-1,3-dipropylxanthine did not reduce NECA-induced I(sc). These results suggest the presence of both A(2A) and A(2B) receptors. NECA did not stimulate a rise in the intracellular Ca2+ concentration ([Ca2+](i)) in single middle ear epithelial cells cultured on glass coverslips. Dibutyryl cAMP (dbcAMP) induced an initial transient increase in I(sc) followed by the sustained plateau. Addition of dbcAMP also caused a transient increase in [Ca2+](i). The protein kinase A inhibitor, N-[2-(p- bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, greatly reduced the increase in the I(sc) responses to NECA. 1,2-Bis-(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid-acetoxymethyl ester influenced neither the NECA- induced increase in I(sc) nor the dbcAMP-induced sustained phase of I(sc), but greatly inhibited the dbcAMP-induced transient increase in I(sc). Glibenclamide, a cystic fibrosis transmembrane conductance regulator (CFTR) channel inhibitor, reduced the NECA-induced I(sc). These results indicate that extracellular adenosine and its analogues activate the cAMP-protein kinase A system, but not intracellular Ca2+-dependent mechanisms, leading to Cl- secretion, possibly through the CFTR Cl-channels in the cultured gerbil middle ear epithelium.

Original languageEnglish
Pages (from-to)103-112
Number of pages10
JournalActa Physiologica Scandinavica
Volume163
Issue number1
DOIs
Publication statusPublished - 1998

Keywords

  • Adenosine
  • CFTR
  • Chloride secretion
  • Middle ear epithelium
  • Short- circuit current
  • cAMP

ASJC Scopus subject areas

  • Physiology

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