Volume 126, Issue 1, Page 11

British Journal of Pharmacology

January 1999, Volume 126, Issue 1, Pages 11 - 18

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Original Article

Effects of Ca²⁺ concentration and Ca²⁺ channel blockers on noradrenaline release and purinergic neuroeffector transmission in rat tail artery
James A. Brock^1,3 & Thomas C. Cunnane²
¹Prince of Wales Medical Research Institute, High Street, Randwick, NSW 2031, Australia     ²University Department of Pharmacology, Mansfield Road, Oxford OX1 3QT

³Author for correspondence

Keywords

Postganglionic sympathetic nerve;   neurotransmitter release;   Ca²⁺ channels;   Ca²⁺ channel blockers;   rat tail artery;   noradrenaline;   adenosine 5'-triphosphate;   electrophysiology;   amperometry

Abstract

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 µM) 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 µM) and omega -agatoxin IVA (40 nM).
5   Nifedipine (10 µM) 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.

Received 9 July 1998; Revised 9 September 1998; Accepted 29 September 1998