Physiological evidence for β3-adrenoceptor in frog (Rana esculenta) heart.
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.
Mazza
Rosa
R
Department of Cell Biology, University of Calabria, Arcavacata di Rende (CS), Italy.
Angelone
Tommaso
T
Pasqua
Teresa
T
Gattuso
Alfonsina
A
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009248:Nadolol / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011893:Rana esculenta; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D000317:Adrenergic alpha-Antagonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D009569:Nitric Oxide; D009248:Nadolol; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol; D010646:Phentolamine