Action of lithium on the adrenergic nerve ending.
The effect of lithium on adrenergic neurotransmission was investigated using the lateral saphenous vein of the dog as a model of the neuroeffector process. Helically cut vein strips were mounted in either an organ bath where tension was recorded or in a superfusion system where both tension and the overflow of [3H]norepinephrine and its metabolites were determined. Lithium was used at both therapeutic (0.5-1.5 mEq/l) and toxic (2.5-14.4 mEq/l) concentrations. Lithium had no effect on basal tension or overflow [3H]norepinephrine. At therapeutic concentrations, the neuronal amine uptake mechanism was augmented, whereas at toxic concentrations monoamine oxidase was inhibited. In therapeutic concentrations, lithium attenuated the response of the adrenergic nerve ending to electrical stimulation (0.5-10 Hz). This response was due in part to the augmentation of the neuronal amine uptake mechanism. At toxic concentrations, responses to low frequency (0.2-1.0 Hz) electrical stimulation were augmented, whereas those at higher frequencies (5-10 Hz) were attenuated. Inhibition of monoamine oxidase by lithium accounted for only a part of the augmented overflow of transmitter and subsequent contractile response since inhibition of monoamine oxidase did not prevent the augmentation by lithium of [3H]norepinephrine overflow. The mechanism by which lithium in both therapeutic and toxic concentrations reduces transmitter overflow and subsequently contractile responses remains to be elucidated. Thus, lithium alters the disposition and release of norepinephrine and, as a result, affects adrenergic neurotransmission.
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D004285:Dogs; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D009411:Nerve Endings / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D012501:Saphenous Vein / Q000294:innervation; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D001679:Biogenic Amines; D008094:Lithium; D010293:Pargyline; D003042:Cocaine; D009638:Norepinephrine