Cultured chick sympathetic neurons: ATP-induced noradrenaline release and its blockade by nicotinic receptor antagonists.
The ATP-induced increase in tritium outflow from cultured chick sympathetic neurons prelabelled with [3H]-noradrenaline was investigated. Seven days-old dissociated cell cultures of embryonic paravertebral ganglia, loaded with [3H]-noradrenaline (0.05 microM), were superfused in the presence of (+)-oxaprotiline and exposed to ATP, ATP-analogues, or 1,1-dimethyl-4-piperazinium (DMPP) for 2 min. ATP (3 microM-3 mM), 2-methylthio-ATP (3-100 microM), as well as DMPP (10 and 100 microM) induced a significant overflow of tritium. The EC50-value of ATP was 20 microM. Both the ATP-induced and the DMPP-induced tritium overflow was Ca(2+)-dependent and sensitive to tetrodotoxin (0.3 microM) and omega-conotoxin (0.1 microM); in addition, it was inhibited by the alpha 2-adrenoceptor agonist 5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline (UK-14,304; 1 microM). The effects of ATP and DMPP were not additive. The ATP-induced as well as the DMPP-induced overflow of tritium was diminished by the P2-purinoceptor antagonists suramin (300 microM) and reactive blue 2 (3 microM); in all 4 cases, the inhibition amouted to approximately 40%. The tritium overflow induced by ATP or DMPP was almost abolished by the nicotinic receptor antagonist mecamylamine (10 microM) and markedly inhibited by hexamethonium (100 microM). Neither ATP nor electrical stimulation caused an overflow of tritium from cultures loaded with [3H]-choline. The results suggest that ATP at mumolar concentrations induces noradrenaline release from cultured chick sympathetic neurons via an action on a subclass of the nicotinic cholinoceptor.
D000227:Adenine Nucleotides / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000320:Adrenergic Fibers / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors
D000227:Adenine Nucleotides; D018733:Nicotinic Antagonists; D013498:Suramin; D000255:Adenosine Triphosphate; D009638:Norepinephrine