Catecholamine release evoked by lithium from the perfused adrenal gland of the cat

Abstract

1 The effect of Li on catecholamine release by cat isolated retrogradely perfused adrenal gland was investigated. Replacement of Na (1 19 mM) by Li in the Krebs solution evoked a progressive increase in the spontaneous release of catecholamines that reached a maximum within 45 min and was Cadependent. This response was specific for Li, since sucrose or choline used as osmotic substitutes for Na, failed to increase the spontaneous release of catecholamines by the adrenal gland. 2 In glands perfused with Li-Krebs for 30 min a sharp secretory response was observed when Li was replaced by sucrose or choline; no such an effect was seen when Li was replaced by Na. 3 Partial replacement of Na by sucrose, in ouabain (10-4M, 10 min) pretreated glands perfused with normal Krebs induced a sharp increase in the catecholamine output whilst replacement by Li produced a significantly lower response. 4 Reintroduction of Ca (2.5 mM, 2 min) in glands previously perfused with Ca-free, Mg-containing Li-Krebs, evoked a sharp increase in catecholamine release. No such an effect was seen when the glands were perfused with Ca-free normal, choline-or sucrose-Krebs. 5 The release of catecholamines evoked by Ca reintroduction in glands previously perfused with Cafree Li-Krebs was directly dependent on the Li concentration and the length of time of the Li loading period. 6 In summary, our results indicate that Li accumulates in the cells and can partially substitute Na in the Na-Ca counter-transport system at the plasma membrane of the chromaffin cell.

Effects of Li+ transport and intracellular binding on Li+/Mg2+ competition in bovine chromaffin cells

“…In human neuroblastoma SH-SY5Y cells and other excitable cells, it has been shown that voltagesensitive Na + channels contribute to Li + influx [30,46], but not in lymphoblastoma cells [36,51]. In bovine chromaffin cells, besides the known Li + influx pathway using voltage-sensitive Na + channels [33,52], we propose here a Ca 2 + -dependent Li + influx pathway in depolarising conditions, where Li + replaces Na + in the Na + /Ca 2 + countertransport.…”

“…Cell depolarisation leads to a massive Ca 2 + entry and to a large increase of intracellular Ca 2 + concentration, which increases the activity of the Na + /Ca 2 + exchanger, known to be a high-capacity, lowaffinity mechanism of Ca 2 + efflux in chromaffin cells [47,48]. It is well known that Li + can replace Na + in the Ca 2 + influx via the Na + /Ca 2 + exchanger pathway in Li +loaded chromaffin cells [33,35] and in rat skeletal muscle cells [49], where Ca 2 + influx is counterbalanced by Li + efflux. In the present case of Li + loading of the chromaffin cells, we propose that the Na + /Ca 2 + exchanger uses the external Na + and Li + to remove intracellular Ca 2 + .…”

Inhibition by lithium of opioid withdrawal-like syndrome and physical dependency in a model of acute cholestasis in mice

“…Therefore, when opioids are withdrawn or naloxone is applied, the neuronal in¯ux of calcium probably becomes too elevated (Bongianni et al, 1986;Baeyens et al, 1987). On the other hand, Li leads to an increase in intracellular calcium content (Abajo et al, 1987), which consequently may attenuate the appearance of increased numbers of voltage-operated calcium channels in the brain. It is therefore not surprising that Li is able to block the development of physical dependency and analgesia.…”

Lithium Inhibits the Development of Physical Dependence to Clonidine in Mice

“…Second, the report that calcium channel blockers attenuated the clonidine withdrawal (Barrios et al 1993), suggests that increased calcium flux may also be involved in the clonidine withdrawal syndrome. Lithium, by increasing the intracellular calcium content (Abajo et al 1987;Branisteanu & Volle 1975), may affect the calcium flux and thus exerts its effect on clonidine withdrawal syndrome. Third, chronic lithium treatment has been reported to lower the binding sites for ligands, for example opioids (Stengaard-Pedersen & Schou 1982), dopamine (Rosenblatt et al 1980), and acetylcholine (Pestronk & Drachman 1980).…”