Effect of omega-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-ty pe calcium blocking agent omega-conotoxin GVIA on stimulation-evoked releas e of noradrenaline from sympathetic nerves in rabbit isolated aorta with re gard to stimulation frequency, extracellular Ca2+ concentration, and transm itter uptake. Rings of rabbit isolated aorta were preloaded with (-)-H-3-no radrenaline and the fractional H-3-overflow evoked by electrical-field stim ulation was determined by liquid scintillation spectrometry. omega-Conotoxi n GVIA (3 x 10(-10) - 3 x 10(-8) M) did not alter the spontaneous H-3-outfl ow omega-Conotoxin GVIA (3 x 10(-10) - 3 x 10(-8) M) caused a slowly develo ping reduction of stimulation-evoked H-3-overflow at 1 and 30 Hz. The Emax for the omega-conotoxin-induced inhibition was less (70%) at 30 Hz than tha t (96%) seen at 1 Hz. Short-term incubation with omega-conotoxin GVIA cause d a subsequent steady-state inhibition. The inhibitory action of omega-cono toxin GVIA (3 x 10(-10) - 3 x 10(-9) M) was inversely related to the extrac ellular Ca2+ concentration (6.5 X 10(-4) - 2.7 x 10(-3) M). Cocaine (3 x 10 (-5) M) plus corticosterone (4 x 10(-5) M), neuronal and extraneuronal upta ke inhibitors, respectively, did not alter the inhibitory effect of omega-c onotoxin GVIA (3 x 10(-9) M) on H-3-overflow evoked by stimulation at a fre quency of either 1 or 30 Hz. It is concluded that omega-conotoxin GVIA acts on prejunctional N-type calcium channels to inhibit stimulation-evoked nor adrenaline release from sympathetic neurone terminals in rabbit aorta. At a high frequency, another subtype calcium channel may possibly be involved. The action of omega-conotoxin GVIA is independent of neuronal and extraneur onal uptake mechanisms for noradrenaline, but dependent on the amount of Ca 2+ to be transported across the neurilemma from the extracellular space int o the neurone.