In preparations from human renal medullary tissue, LiCl in concentrations below 50mM slightly increased or had no significant effect on the basal activity of adenylate cyclase or on the activity stimulated by submaximal concentrations of vasopressin. After addition of 200mM NaCl or 200 mM NaCl plus 200 mM urea, LiCl had a marked inhibitory effect on the stimulationof adenylate cyclase by vasopressin but not on the basal activity of this enzyme. This inhibitory effect could not be overcome by supramaximal levels of vasopressin. The adenylate cyclasestimulated by sodium fluoride was only slightly inhibited by LiCl. Adenylate cyclase stimulatedby structural analogues of vasopressin with modifications in amino acids 3 and 8 was inhibited by LiCl in the same way as when it was stimulated by the natural hormone. In contrast to this, in a medium of similar osmolarity used for the adenylate cyclase assay, LiCl in concentrations below 50 nM did not influence activity of cyclic AMPphosphodiesterase(5 × 10-7to5 × 10-4Mcyclic AMP as substrate). Cyclic AMP-dependent protein kinase wasslightly inhibited by 30 mM LiCl but this inhibition was much less pronounced than that of vasopressin-sensitive adenylate cyclase. The results suggest that lithium blocks the antidiuretic effect of vasopressin primarily by inhibition of renal medullary adenylate cyclase in a medium of high osmolarity. Some features of this in vitro lithium effect also suggest that this ion might serve as a suitable inhibitor of high vasopressin levels in vivo. (Endocrinology95: 1359, 1974)
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Thomas P. Douša (1974) studied this question.