Effects of Ca2+ concentration and Ca2+ channel blockers on noradrenaline release and purinergic neuroeffector transmission in rat tail artery.
1. The effects of Ca2+ concentration and Ca2+ channel blockers on noradrenaline (NA) and adenosine 5'-triphosphate (ATP) release from postganglionic sympathetic nerves have been investigated in rat tail arteries in vitro. Intracellularly recorded excitatory junction potentials (e.j.ps) were used as a measure of ATP release and continuous amperometry was used to measure NA release. 2. Varying the extracellular Ca2+ concentration similarly affected the amplitudes of e.j.ps and NA-induced oxidation currents evoked by trains of ten stimuli at 1 Hz. 3. The N-type Ca2+ blocker, omega-conotoxin GVIA (omega-CTX GVIA, 0.1 microM) reduced the amplitudes of both e.j.ps (evoked by trains of ten stimuli at 1 Hz) and NA-induced oxidation currents (evoked by trains of ten stimuli at 1 Hz and 50 stimuli at 10 Hz) by about 90%. 4. The omega-CTX GVIA resistant e.j.ps and NA-induced oxidation currents evoked by trains of 50 stimuli at 10 Hz were abolished by the non-selective Ca2+ channel blocker, Cd2+ (0.1 mM), and were reduced by omega-conotoxin MVIIC (0.5 microM) and omega-agatoxin IVA (40 nM). 5. Nifedipine (10 microm) had no inhibitory effect on omega-CTX GVIA resistant e.j.ps and NA-induced oxidation currents. 6. Thus both varying Ca2+ concentration and applying Ca2+ channel blockers results in similar effects on NA and ATP release from postganglionic sympathetic nerves. These findings are consistent with the hypothesis that NA and ATP are co-released together from the sympathetic nerve terminals.
Prince of Wales Medical Research Institute, Randwick, NSW, Australia.
J A
JA
Brock
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Cunnane
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013623:Tail; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D010455:Peptides; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D000255:Adenosine Triphosphate; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine