Noradrenaline release from rat sympathetic neurons evoked by P2-purinoceptor activation.
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 mumol/l, respectively. 2-Methylthio-ATP was equipotent to ATP in inducing 3H-overflow. ADP (100 mumol/l), when applied for 2 min, also caused a small 3H-overflow, but alpha, beta-methylene-ATP (100 mumol/l), AMP (100 mumol/l), R(-)N6-(2-phenylsiopropyl)-adenosine (R(-)-PIA; 10 mumol/l) and 5'-N-ethylcarboxamidoadenosine (NECA; 1 mumol/l) did not. The 3H-overflow induced by 10 s applications of 100 mumol/l ATP was abolished by suramin (100 mumol/l) and reduced by about 70% by reactive blue 2 (3 mumol/l). Electrically evoked overflow, in contrast, was slightly enhanced by suramin, but not modified by reactive blue 2. Xanthine amine congener (10 mumol/l) and hexamethonium (10 mumol/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 mumol/l) abolished electrically evoked 3H-overflow but inhibited ATP-induced overflow by only 70%. The alpha 2-adrenoceptor agonist UK 14,304 at a concentration of 1 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Boehm
S
S
Institute of Neuropharmacology, University of Vienna, Austria.
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D002118:Calcium; D002478:Cells, Cultured; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000378:metabolism*; D058910:Purinergic P2 Receptor Agonists; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D058910:Purinergic P2 Receptor Agonists; D011810:Quinoxalines; D018048:Receptors, Purinergic P2; D014227:Triazines; D014970:Xanthines; D013779:Tetrodotoxin; D000068438:Brimonidine Tartrate; C012842:Cibacron Blue F 3GA; D013498:Suramin; D000255:Adenosine Triphosphate; C051869:8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine; D002118:Calcium; D009638:Norepinephrine