Abstract
The effects of ATP and analogues on the release of previously incorporated 3H-noradrenaline were studied in cultured sympathetic neurons derived from superior cervical ganglia of neonatal rats. Electrical field stimulation (40 mA at 3 Hz) of the neurons for 10 s markedly enhanced the outflow of tritium. ATP applied for 5 s to 2 min at concentrations of 0.01 to 1 mmol/l caused a time- and concentration-dependent overflow with half maximal effects at about 10 s and 100 μmol/l, respectively. 2-Methylthio-ATP was equipotent to ATP in inducing 3H-overflow. ADP (100 μmol/l), when applied for 2 min, also caused a small 3H-overflow, but α, β-methylene-ATP (100 μmol/l), AMP (100 μmol/l), R(−)N6-(2-phenylsiopropyl)-adenosine (R(−)-PIA; 10 μmol/l) and 5′-N-ethylcarboxamidoadenosine (NECA; 1 μmol/l) did not. The 3H-overflow induced by 10 s applications of 100 μmol/l ATP was abolished by suramin (100 μmol/l) and reduced by about 70% by reactive blue 2 (3 μmol/l). Electrically evoked overflow, in contrast, was slightly enhanced by suramin, but not modified by reactive blue 2. Xanthine amine congener (10 μmol/l) and hexamethonium (10 μmol/l) did not alter ATP-evoked release. Removal of extracellular Ca2+ from the medium reduced ATP- and electrically induced overflow by about 95%. Tetrodotoxin (1 μmol/l) abolished electrically evoked 3H-overflow but inhibited ATP-induced overflow by only 70%. The α2-adrenoceptor agonist UK 14,304 at a concentration of 1 μmol/l diminished both electrically and ATP-evoked tritium overflow by approximately 70%. These results indicate that activation of P2-purinoceptors stimulates noradrenaline release from rat sympathetic neurons. The release resembles electrically induced transmitter release, but additional mechanisms may contribute.
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Correspondence to: S. Boehm at the above address
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Boehm, S. Noradrenaline release from rat sympathetic neurons evoked by P2-purinoceptor activation. Naunyn-Schmiedeberg's Arch Pharmacol 350, 454–458 (1994). https://doi.org/10.1007/BF00173013
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DOI: https://doi.org/10.1007/BF00173013