Non-genomic actions of 17beta-oestradiol in mouse pancreatic beta-cells are mediated by a cGMP-dependent protein kinase

J Physiol. 1999 Dec 1;521 Pt 2(Pt 2):397-407. doi: 10.1111/j.1469-7793.1999.00397.x.


1. Intracellular calcium concentration ([Ca2+]i) was measured in mouse whole islets of Langerhans using the calcium-sensitive fluorescent dye Indo-1. 2. Application of physiological concentrations of 17beta-oestradiol in the presence of a stimulatory glucose concentration (8 mM) potentiated the [Ca2+]i signal in 83 % of islets tested. Potentiation was manifested as either an increase in the frequency or duration of [Ca2+]i oscillations. 3. The effects caused by 17beta-oestradiol were mimicked by the cyclic nucleotide analogues 8-bromoguanosine-3',5'-cyclic monophosphate (8-Br-cGMP) and 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP). 4. Direct measurements of both cyclic nucleotides demonstrated that nanomolar concentrations of 17beta-oestradiol in the presence of 8 mM glucose increased cGMP levels, yet cAMP levels were unchanged. The increment in cGMP was similar to that induced by 11 mM glucose. 5. Patch-clamp recording in intact cells showed that 8-Br-cGMP reproduced the inhibitory action of 17beta-oestradiol on ATP-sensitive K+ (KATP) channel activity. This was not a membrane-bound effect since it could not be observed in excised patches. 6. The action of 17beta-oestradiol on KATP channel activity was not modified by the specific inhibitor of soluble guanylate cyclase (sGC) LY 83583. This result indicates a likely involvement of a membrane guanylate cyclase (mGC). 7. The rapid decrease in KATP channel activity elicited by 17beta-oestradiol was greatly reduced using Rp-8-pCPT-cGMPS, a specific blocker of cGMP-dependent protein kinase (PKG). Conversely, Rp-cAMPS, which inhibits cAMP-dependent protein kinase (PKA), had little effect. 8. The results presented here indicate that rapid, non-genomic effects of 17beta-oestradiol after interaction with its binding site at the plasma membrane of pancreatic beta-cells is a cGMP-dependent phosphorylation process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Adenosine Triphosphate / physiology
  • Animals
  • Calcium / metabolism
  • Calcium Signaling / physiology
  • Cell Membrane / chemistry
  • Cell Membrane / enzymology
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / metabolism*
  • Cyclic GMP / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Estradiol / pharmacology*
  • Fluorescent Dyes
  • Indoles
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / enzymology*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Patch-Clamp Techniques
  • Potassium Channels / physiology
  • Thionucleotides / pharmacology


  • 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate
  • Enzyme Inhibitors
  • Fluorescent Dyes
  • Indoles
  • Potassium Channels
  • Thionucleotides
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Estradiol
  • Adenosine Triphosphate
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Cyclic GMP
  • indo-1
  • Calcium