Lithium ions inhibit function of low- but not high-affinity muscarinic receptors of murine neuroblastoma cells (clone N1E-115).

Abstract:

: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.

journal_title

Psychopharmacology

authors

Kanba S,Pfenning M,Richelson E

doi

10.1007/BF00427901

subject

Has Abstract

pub_date

1985-01-01 00:00:00

pages

413-6

issue

4

eissn

0033-3158

issn

1432-2072

journal_volume

86

pub_type

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