The effect of exogenous adenosinetriphosphate on the choline-calcium stimulated release of 3H-norepinephrine in rat heart ventricle slices.
Evidence in this and other reports from this laboratory suggest that adrenergic nerves in rat heart ventricle slices incubated in a Na+-deprived (choline+) medium containing Ca++ (Ch+--Ca++), transport (by a cocaine-sensitive mechanism) 3H-norepinephrine outwardly from synaptic vesicles attached or fused to the plasma membrane. The 3H-amine secretion was not inhibited by probenecid, an anion transport inhibitor which may prevent exocytosis. The 3H-amine release was rapidly inhibited by exogenous nucleotides ATP, UTP, and GTP greater than ADP greater than AMP greater than the nucleoside adenosine. Magnesium++ tended to increase and reserpine to decrease the effect of ATP. Neither increasing the [Ca++] nor [Mg++] (to compete with Ca++ for ATP) decreased the effect of 3 mM ATP. After secretion began, lowering the Ca++ concentration by ommission, or by the inclusion of either a low concentration of EDTA or the Ca++-binding, but non-energy-conserving synthetic analogs of ATP: AMP--PCP and AMP--PNP, gradually lowered the rates of secretion. By comparison, the rapid effects of the energy-conserving nucleotides suggested that their effects were at least partially independent of chelation, and were energy dependent. ATP, unlike cocaine, did not inhibit the uptake of NE in a Krebs HCO3 medium. Inhibition of (Na+ + K+)-ATPase by ouabain neither inhibited the release by Ch+--Ca++, nor antagonizes the release inhibiting effect of ATP. Hence, ATP did not increase apparent retention of NE by stimulating the uptake of released NE. The ATP-inhibited secretion was not increased by theophylline.
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000494:pharmacology*; D002794:Choline / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009489:Neurosecretion / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000266:Adenylyl Imidodiphosphate; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D000255:Adenosine Triphosphate; D008274:Magnesium; D002794:Choline; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium; D009638:Norepinephrine