The effect of lithium (Li) on the stimulation of adenylate cyclase by prostaglandin E1(PGE1) was examined. In platelet sonicates, Li, as well as sodium (Na), potassium (K), and rubidium (Rb) significantly reduced the PGE1-induced stimulation of adenylate cyclase in a dose-dependent manner. The inhibition due to Rb was significantly less than that produced by the other cations; at a high concentration, 64 mM, Li was a more potent inhibitor than the other cations. In intact platelets, only Li reduced the PGE1-enhanced accumulation of [3H]cyclic AMP, K and Rb being ineffective. As little as 1 mM Li significantly reduced the stimulatory effect of PGE1 on [3H]cyclic AMP production in this sytem. The inhibition produced by Li was not blocked by phentolamine, whereas phentolamine did block the inhibition due to norepinephrine (NE). Magnesium enhanced the stimulatory effect of PGE1 on the production of labeled cyclic AMP in intact platelets and antagonized the inhibition produced by Li on this process. These data show that Li antagonizes PGE1- induced stimulation of platelet adenylate cyclase at a site distinct from that at which NE acts.
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