Physiological evidence for β3-adrenoceptor in frog (Rana esculenta) heart

Gen Comp Endocrinol. 2010 Nov 1;169(2):151-7. doi: 10.1016/j.ygcen.2010.08.003. Epub 2010 Aug 13.


β3-Adrenergic receptors (ARs) have been recently identified in mammalian hearts where, unlike β1- and β2-ARs, induce cardio-suppressive effects. The aim of this study was to describe β3-AR role in the frog (Rana esculenta) heart and to examine its signal transduction pathway. The presence of β3-AR, by using Western blotting analysis, has been also identified. BRL(37344), a selective β3-AR agonist, induced a dose-dependent negative inotropic effect at concentrations from 10(-12) to 10(-6)M. This effect was not modified by nadolol (β1/β2-AR antagonist) and by phentolamine (α-AR antagonist), but it was suppressed by the β3-AR-specific antagonist SR(59230) and by exposure to the Gi/o proteins inhibitor Pertussis Toxin. In addition, the involvement of EE-NOS-cGMP-PKG/PDE2 pathway in the negative inotropism of BRL(37344) has been assessed. BRL(37344) treatment induced eNOS and Akt phosphorylation as well as an increase of cGMP levels. β3-ARs activation induce a non-competitive antagonism against ISO stimulation which disappeared in presence of PKG and PDE2 inhibition. Taken together our findings provide, for the first time in the frog, a role for β3-ARs in the cardiac performance modulation which involves Gi/o protein and occurs via an EE-NO-cGMP-PKG/PDE2 cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Adrenergic beta-3 Receptor Antagonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Blotting, Western
  • Cyclic AMP / metabolism
  • Cyclic GMP / metabolism
  • Female
  • Heart / drug effects
  • Isoproterenol / pharmacology
  • Male
  • Myocardium / metabolism*
  • Nadolol / pharmacology
  • Nitric Oxide / metabolism
  • Phentolamine / pharmacology
  • Propanolamines / pharmacology
  • Rana esculenta
  • Receptors, Adrenergic, beta-2 / metabolism
  • Receptors, Adrenergic, beta-3 / metabolism*


  • 3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate
  • Adrenergic alpha-Antagonists
  • Adrenergic beta-3 Receptor Antagonists
  • Adrenergic beta-Antagonists
  • Propanolamines
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-3
  • Nitric Oxide
  • Nadolol
  • Cyclic AMP
  • Cyclic GMP
  • Isoproterenol
  • Phentolamine