P. Narayan et al., Phosphatase inhibitor cantharidin blocks adenosine A(1) receptor anti-adrenergic effect in rat cardiac myocytes, AM J P-HEAR, 278(1), 2000, pp. H1-H7
Citations number
32
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Experiments were performed to examine whether the protein phosphatase inhib
itor cantharidin blocks the antiadrenergic effect of adenosine A(1) recepto
r stimulation. In electrically stimulated adult rat ventricular myocytes lo
aded with the intracellular calcium concentration ([Ca2+](i)) indicator flu
o-3, isoproterenol(10 nM) increased systolic [Ca2+](i) by 46%, increased tw
itch amplitude by 56%, and increased total cellular cAMP content by 140%. T
he adenosine A(1) receptor agonist 2-chloro-N-6-cyclopentlyadenosine (CCPA)
reduced isoproterenol-stimulated [Ca2+](i) and contractility by 87 and 80%
, respectively, but reduced cAMP content by only 18%. Cantharidin had no ef
fects on myocyte [Ca2+](i), contractility, or cAMP in the absence or presen
ce of isoproterenol but blocked the effects of CCPA on [Ca2+](i) and contra
ctility by similar to 44%. Cantharidin had no effect on CCPA attenuation of
isoproterenol-induced increases in cAMP. Pretreatment with CCPA also reduc
ed the increase in contractile parameters produced by the direct cAMP-depen
dent protein kinase A (PKA)activator 8-bromocAMP. These results suggest tha
t activation of protein phosphatases mediate, in part, the anti-adrenergic
effect of adenosine A(1) receptor activation in ventricular myocardium.