Vesicular site of action of lithium ion in choline-calcium stimulated adrenergic nerve endings of rat heart.
Reports from this laboratory have suggested that the secretion of norepinephrine (NE) in slices of ventricle from the rat heart, incubated in a medium of choline and Ca2+ (Ch+-Ca2+) deprived of Na+, is mediated by the outward transport of NE (blocked by cocaine) from synaptic vesicles fused or attached to the axolemma. Lithium (and reserpine), block the Mg2+-ATP-stimulated uptake of NE by isolated synaptic vesicles (Slotkin, Seidler, Whitmore, Salvaggio, and Lau, 1978). Hence, a hypothesis to be tested was that lithium ions would increase secretion of NE stimulated by Ch+-Ca2+. By contrast, amines mobilized by lithium ions (or reserpine) in control nerves would be deaminated. Experiments showed that lithium-Krebs increased the excretion of [3H]deaminated metabolites of [3H]NE. A much smaller quantity of [3H]NE was released by a process that was independent of Ca2+ and weakly inhibited by cocaine. When combined with Ch+Ca2+, lithium ions, in concentrations that were known to block uptake in isolated vesicles, induced a Ca2+-dependent secretion of [3H]amines. A small quantity of [3H]deaminated metabolites was excreted. Both processes were strongly inhibited by both cocaine and desipramine. Both reserpine (Bogdanski, 1982) and lithium ions blocked the inhibitory effect of exogenous ATP (2 mM) on secretion induced by Ch+-Ca2+. This effect indicated a proximity of vesicles to the axolemma. The effects of lithium ions could be explained by the hypothesis if lithium prevented storage of [3H]NE in vesicles by blocking the Mg2+ + ATP-dependent amine pump in vesicle membranes.
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D002794:Choline / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects*; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects*
D001679:Biogenic Amines; D000255:Adenosine Triphosphate; D008094:Lithium; D003042:Cocaine; D002794:Choline; D002118:Calcium; D003891:Desipramine