Electrochemical and electrophysiological characterization of neurotransmitter release from sympathetic nerves supplying rat mesenteric arteries.
1. Characteristic features of noradrenaline (NA) and adenosine 5'-triphosphate (ATP) release from postganglionic sympathetic nerves in rat small mesenteric arteries in vitro have been investigated on an impulse-by-impulse basis. NA release was measured using continuous amperometry and ATP release was monitored by intracellular recording of excitatory junction potentials (e.j.ps). 2. Electrical stimuli evoked transient increases in oxidation current. During trains of ten stimuli at 0.5 - 4 Hz there was a depression in the amplitude of oxidation currents evoked following the first stimulus in the train. 3. The neuronal NA uptake inhibitor, desmethylimipramine (1 microM), increased the amplitude of the summed oxidation current evoked by ten stimuli at 1 Hz and slowed the decay of oxidation currents evoked by trains of ten stimuli at 1 and 10 Hz. 4. The alpha2-adrenoceptor antagonist, idazoxan (1 microM), increased the amplitudes of the oxidation currents evoked during trains of ten stimuli at 0.5 - 10 Hz but had no effect on the oxidation currents evoked by the first stimulus in the train. 5. Idazoxan (1 microM) increased the amplitude of all e.j.ps evoked during trains of stimuli at 0.5 and 1 Hz. In addition, the facilitatory effect of idazoxan on e.j.ps was significantly greater than that on oxidation currents. 6. The findings indicate that NA release from sympathetic nerves supplying small mesenteric arteries is regulated by activation of presynaptic alpha2-adrenoceptors and that clearance of released NA in this tissue depends, in part, upon neuronal uptake. The different effects of idazoxan on the oxidation currents and e.j.ps may indicate that the release of NA and ATP is differentially modulated.
Dunn
W R
WR
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, U.K.
Brock
J A
JA
Hardy
T A
TA
D000255:Adenosine Triphosphate / Q000378:metabolism; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004553:Electric Conductivity; D004558:Electric Stimulation; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D019329:Idazoxan / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D002104:Cadmium; D013779:Tetrodotoxin; D000255:Adenosine Triphosphate; D003891:Desipramine; D003345:Corticosterone; D009638:Norepinephrine; D019329:Idazoxan