Coordinated Release of ATP and ACh from Cholinergic Synaptosomes and Its Inhibition by Calmodulin Antagonists

Isolated cholinergic synaptosomes from elasmobranch electric organ release both ACh and ATP when depolarized in the presence of calcium. The conditions that trigger ATP release are the same as those known to stimulate neurosecretion. The ratio of ACh to ATP released is the same as that found in purified elasmobranch synaptic vesicles. Both ACh and ATP release are inhibited either by the removal of extracellular calcium or the addition of the "calmodulin antagonist" trifluoperazine (TFP). Taken together, these data suggest that both ACh and ATP are released by exocytosis from synaptic vesicles within nerve terminals. A number of drugs, collectively known as calmodulin antagonists, were examined for their effect on neurosecretion. TFP completely inhibited secretion in a rapid and reversible manner. Other related drugs had similar effects, though with relative efficacies different from those reported for inhibiting calmodulin. It therefore seems likely that a calmodulin-like component of the nerve terminal, distinct from calmodulin itself, is essential for the process of neurosecretion.