Mutual occlusion of P2X ATP receptors and nicotinic receptors on sympathetic neurons of the guinea-pig.
1. The interaction of ion channels activated by nicotinic receptor agonists with ion channels gated by extracellular ATP (i.e. P2X receptors) was studied on sympathetic neurons acutely dissociated from coeliac ganglia of the guinea-pig. Patch clamp methods were used to measure the inward current generated through these non-selective cationic channels under voltage clamp. 2. At the whole cell level, the specific nicotinic receptor agonists nicotine (5-100 microM) or cytisine (50-75 microM) and the P2X receptor agonists ATP (0.1-7 microM) or alpha,beta-methylene ATP (6 microM) were examined separately and in the presence of the other receptor activator. When a nicotinic and P2X receptor agonist were applied together, mutually occlusive effects were generally observed. This occurred even with concentrations of agonists that in themselves generated little to no inward current. 3. The occlusive effects of nicotinic agonists on ATP-gated currents were blocked by the nicotinic receptor/ion channel blocker hexamethonium (150 microM). The occlusive effects of ATP analogues on inward currents generated by nicotinic agonists were blocked by the P2X receptor antagonist suramin (100 microM). 4. Mutual occlusion of the effects of nicotinic agonists and ATP analogues were also observed when currents through single channels were studied in excised (outside-out) patches. 5. The results suggest that nicotinic receptors and P2X ATP receptors do not act independently in these sympathetic neurons.
Searl
T J
TJ
Department of Molecular Pharmacology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Redman
R S
RS
Silinsky
E M
EM
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011978:Receptors, Nicotinic / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D018722:Nicotinic Agonists; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011978:Receptors, Nicotinic; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D009538:Nicotine; D000255:Adenosine Triphosphate