SODIUM-FLUORIDE ATTENUATES THE NEGATIVE INOTROPIC EFFECTS OF MUSCARINIC M(2) AND ADENOSINE RECEPTOR AGONISTS

Sodium fluoride increased the force of contraction in isolated guinea- pig papillary muscles concentration dependently, starting at 3 mmol/l. Sodium fluoride inhibited phosphorylase phosphatase activity in homog enates from guinea pig hearts, starting at 1 mmol/l. The positive inot ropic effect of 3 mmol/l sodium fluoride was not accompanied by an inc rease in cAMP content in guinea-pig papillary muscles. In papillary mu scles, carbachol or (-)-N-6-phenylisopropyladenosine reduced the posit ive inotropic effect of isoprenaline (10 nmol/l) or the phosphodiester ase inhibitor 3-isobutyl-1-methylxanthine (60 mu mol/l). These negativ e inotropic effects of carbachol and (-)-N-6-phenylisopropyladenosine were attenuated by additional sodium fluoride (3 mmol/l). It is conclu ded that sodium fluoride can impair the signal transduction of muscari nic M(2) (carbachol) and adenosine receptor ((-)-N-6-phenylisopropylad enosine) agonists. This effect of sodium fluoride could support the hy pothesis that the cardiac effects of muscarinic M(2) and adenosine rec eptor agonists involve, at least in part, the activation of phosphates .