Effects of lithium on cAMP generation in cultured rat inner medullary collecting tubule cells

Effects of lithium on cAMP generation in cultured rat inner medullary collecting tubule cells. The effects of lithium (Li) on the cAMP system in rat inner medullary collecting tubule cells were studied. While acute exposure to 5mM Li was without effect, 10mM, 25mM and 50mM Li significantly decreased AVP-stimulated cAMP formation. In contrast, cells grown in 5mM Li for 72hours which caused no morphologic changes enhanced cAMP formation (fmol/μg protein) in response to both 10nM AVP (114.5 ± 9.2 vs. 71.6 ± 7.4,P > 0.005) and 100nM AVP (182 ± 14 vs. 120 ± 8.3, P < 0.001), N = 16. A similar enhancement was observed when cAMP formation was stimulated by a post-receptor agonist, cholera toxin. The role of eicosanoids was examined with 5 μM meclofenamate which reversed Li-enhanced cAMP formation in response to both AVP and cholera toxin. To define the eicosanoid responsible, cyclooxygenase products were measured. Prostaglandin E2; and thromboxane B2 synthesis were unchanged by Li, but the production of prostacyclin was significantly (P < 0.02) increased. Prostacyclin (3 μM) mimicked the effect of Li to enhance the response to 10nM AVP as cAMP levels increased from 100 ± 11 to 173 ± 13, P < 0.05. The experiments suggest that acute exposure of Li at concentrations of 10mM or greater inhibit cAMP formation but prolonged Li exposure enhances cAMP formation by increasing the formation of prostacyclin.