Similarities of Li+ and low Ca2+ in the modulation of secretion by parathyroid cells in vitro.

Parathyroid hormone (PTH) release from parathyroid cells in vitro was found to be stimulated by the presence of extracellular lithium ions through a specific secretory response which was comparable to that elicited by low extracellular Ca2+. Li+ (5-40 mM) caused a dramatic increase in the basal PTH secretory rate (up to 2.5-fold), as well as a further enhancement of the low Ca2+-stimulated PTH secretory rate (up to 0.5-fold). Cellular mediators commonly implicated in hormone release from endocrine cells, such as Ca2+ influx, cAMP, and changes in the activity of (Na+, K+) ATPase, were not involved in Li+-stimulated PTH release. The PTH secretory response induced by Li+ was fully maintained in the virtual absence of external Ca2+. Parathyroid cellular cAMP levels were unchanged in buffers varied with respect to both Li+ and Ca2+ and remained constant throughout the time course of Li+ uptake. Ouabain, in concentrations sufficient to block Na+, K+ activity, was also without effect on PTH release elicited by Li+. To identify the site and possible effectors of this stimulatory effect, experimental protocols were devised to modulate the level of intracellular Li+ at constant external Li+ concentrations. These results showed that the enhancement of PTH secretion by Li+ was independent of a 3-fold variation in intracellular Li+, but was directly related to the external Li+ concentration. This and previous evidence suggest that the regulation of PTH secretion by both lithium and calcium ions does not require their transmembrane influx but occurs instead in the parathyroid plasma membrane.