Effect of ω‐Conotoxin GVIA on Noradrenaline Release from Postganglionic Sympathetic Neurones in Rabbit Aorta

The aim of the present work was to examine the effect of the selective N‐type calcium blocking agent ω‐conotoxin GVIA on stimulation‐evoked release of noradrenaline from sympathetic nerves in rabbit isolated aorta with regard to stimulation frequency, extracellular Ca 2+ concentration, and transmitter uptake. Rings of rabbit isolated aorta were preloaded with (‐)‐ 3 H‐noradrenaline and the fractional 3 H‐overflow evoked by electrical‐field stimulation was determined by liquid scintillation spectrometry. ω‐Conotoxin GVIA (3×10 −10 – 3×10 −8 M) did not alter the spontaneous 3 H‐outflow. ω‐Conotoxin GVIA (3×10 −10 – 3×10 −8 M) caused a slowly developing reduction of stimulation‐evoked 3 H‐overflow at 1 and 30 Hz. The E max for the ω‐conotoxin‐induced inhibition was less (70%) at 30 Hz than that (96%) seen at 1 Hz. Short‐term incubation with ω‐conotoxin GVIA caused a subsequent steady‐state inhibition. The inhibitory action of ω‐conotoxin GVIA (3×10 −10 – 3×10 −9 M) was inversely related to the extracellular Ca 2+ concentration (6.5×10 −4 – 2.7×10 −3 M). Cocaine (3×10 −5 M) plus corticosterone (4×10 −5 M), neuronal and extraneuronal uptake inhibitors, respectively, did not alter the inhibitory effect of ω‐conotoxin GVIA (3×10 −9 M) on 3 H‐overflow evoked by stimulation at a frequency of either 1 or 30 Hz. It is concluded that ω‐conotoxin GVIA acts on prejunctional N‐type calcium channels to inhibit stimulation‐evoked noradrenaline release from sympathetic neurone terminals in rabbit aorta. At a high frequency, another subtype calcium channel may possibly be involved. The action of ω‐conotoxin GVIA is independent of neuronal and extraneuronal uptake mechanisms for noradrenaline, but dependent on the amount of Ca 2+ to be transported across the neurilemma from the extracellular space into the neurone.