A physiological requirement of Na+ for the regulation of cAMP levels in intact NG108-15 cells

The ability of Dala²met⁵NH₂ enkephalin, carbachol and norepine-phrine to reduce prostaglandin E₁ (PGE₁) elevated intracellular cAMP concentrations in NG108-15 cells is dependent upon extracellular Na⁺. The selectivity for monovalent cations in this process is Na⁺ {all equal to} Li⁺ ≫K⁺ > choline⁺, and the apparent K_m for Na⁺ is 30-40 mM. Extracellular ions, with a similar selectivity, are also required to maintain maximal basal and elevated cAMP concentrations. However, the fold elevation in cAMP produced by PGE₁ and/or 2Cl-adenosine is not reduced when [Na⁺]_out is replaced by [Li⁺]_out, [K⁺]_out or [Choline⁺]_out. Therefore, [Na⁺]_out is presumably not necessary for activation of adenylate cyclase by PGE₁ or 2Cl-adenosine. The elimination of free [Ca⁺⁺] causes a slight reduction in the ability of CCh to decrease cAMP concentrations. Ca Ca⁺⁺ flux does not seem to be required for either receptor-mediated elevation or reduction of cAMP as these two processes are unaffected by D600 or verapamil. The data presented support the hypothesis that the general transfer of inhibitory information from membrane receptors to adenylate cyclase involves a regulatory unit which is sensitive to Na⁺.