Lithium ions inhibit function of low- but not high-affinity muscarinic receptors of murine neuroblastoma cells (clone N1E-115).
Murine neuroblastoma cells (clone N1E-115) possess both high- and low-affinity muscarinic receptors. The low-affinity muscarinic receptor, when stimulated, initiates the formation of cyclic GMP by activating the enzyme guanylate cyclase; whereas stimulation of the high-affinity receptor inhibits prostaglanding E1-mediated cyclic AMP formation by inhibiting the enzyme adenylate cyclase. We have reported that lithium ion (Li+) inhibits cyclic GMP formation mediated by the muscarinic receptor agonist, carbachol, in a concentration-dependent manner and that neither ammonium nor sodium ions have such an effect. We extended this study to show that Li+ was an apparently noncompetitive inhibitor of the low-affinity muscarinic receptor with an IC50(+/- SEM) = 13.6 +/- 0.8 mM. In addition, Li+ with a similar IC50 inhibited the cyclic GMP response in intact cells to sodium azide, which is thought to stimulate guanylate cyclase directly. Moreover, though Li+ was found to have a slight inhibitory effect on prostaglandin E1-stimulated cyclic AMP formation (15% inhibition at 10 mM), it had no effect on the function of the high-affinity muscarinic receptor in intact murine neuroblastoma cells.
Kanba
S
S
Pfenning
M
M
Richelson
E
E
D000527:Alprostadil; D000818:Animals; D001386:Azides / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis; D008094:Lithium / Q000494:pharmacology*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects*; D019810:Sodium Azide
D001386:Azides; D011458:Prostaglandins E; D011976:Receptors, Muscarinic; D002217:Carbachol; D019810:Sodium Azide; D008094:Lithium; D000527:Alprostadil; D006152:Cyclic GMP