The action of extracellular cations on the release of the sympathetic transmitter from peripheral nerves.

1. The noradrenaline stores in the sympathetic nerve endings of the cat colon were labelled in vivo with (+/-)-[7-(3)H]noradrenaline (500 muc, 11.3 mug) injected 3 hr before killing.2. The colon was removed and immersed in an organ bath containing Krebs solution. The vascular bed was perfused from the inferior mesenteric artery to the colic vein.3. The effects of Ca(2+), Ba(2+) and Mg(2+) on the output of [(3)H]noradrenaline and [(3)H]metabolites in the venous effluent were measured before and after electrical stimulation of the post-ganglionic inferior mesenteric nerves at 10 impulses/sec.4. Nerve stimulation increased the efflux of [(3)H]noradrenaline when the perfusion fluid contained Ca(2+). Variations in Ca(2+) concentration (1.5-10 mM) did not affect this response.5. Removal of Ca(2+) from the fluid passing through the vascular bed (and therefore from the region of the sympathetic nerve terminals), abolished the output of [(3)H]noradrenaline in response to nerve stimulation. There was no change when phenoxybenzamine was added to prevent the binding of transmitter on to post-synaptic receptors on the effector organ.6. The output of transmitter was not changed when Ca(2+) was present in the blood vessels of the colon even though it was removed from the solution in contact with the remainder of the tissue.7. Nerve stimulation released [(3)H]noradrenaline when Ba(2+) was used as a substitute for Ca(2+); Mg(2+) was not an effective substitute for Ca(2+) as then nerve stimulation did not increase the output of radioactive noradrenaline or metabolites.8. Ba(2+) also increased the resting output of [(3)H]noradrenaline in the absence of nerve stimulation. Addition of Ca(2+) or Mg(2+) did not change this spontaneous release but it was augmented by removal of Ca(2+).9. It is concluded that Ca(2+) is essential for release of the sympathetic transmitter by nerve stimulation but not for the spontaneous output that occurs in the absence of nervous activity. The site of action of Ca(2+) is considered to be the terminals of adrenergic fibres.