Sodium fluoride attenuates the negative inotropic effects of muscarinic M2 and adenosine receptor agonists.
Sodium fluoride increased the force of contraction in isolated guinea-pig papillary muscles concentration dependently, starting at 3 mmol/1. Sodium fluoride inhibited phosphorylase phosphatase activity in homogenates from guinea pig hearts, starting at 1 mmol/1. The positive inotropic effect of 3 mmol/1 sodium fluoride was not accompanied by an increase in cAMP content in guinea-pig papillary muscles. In papillary muscles, carbachol or (-)-N(6)-phenylisopropyladenosine reduced the positive inotropic effect of isoprenaline (10 nmol/1) or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (60 mu mol/1). These negative inotropic effects of carbachol and (-)-N(6)-phenylisopropyladenosine were attenuated by additional sodium fluoride (3 mmol/l). It is concluded that sodium fluoride can impair the signal transduction of muscarinic M2 (carbachol) and adenosine receptor (-)-N(6)-phenylisopropyladenosine) agonists. This effect of sodium fluoride could support the hypothesis that the cardiac effects of muscarinic M2 and adenosine receptor agonists involve, at least in part, the activation of phosphatases.
Neumann
J
J
Abteilung Allgemeine Pharmakologie, Universitats-Krankenhaus Eppendorf, Hamburg, Germany.
Kaspareit
G
G
Kirchhefer
U
U
Scholz
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis; D003864:Depression, Chemical; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists; D012969:Sodium Fluoride / Q000494:pharmacology*
D018721:Muscarinic Agonists; D058906:Purinergic P1 Receptor Agonists; D010660:Phenylisopropyladenosine; D002217:Carbachol; D012969:Sodium Fluoride; D000242:Cyclic AMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine