Differential effects of lithium on agonist-stimulated inositol polyphosphate formation in rat cerebral cortex slices: Selective actions on muscarinic cholinergic responses.
The effect of lithium ions on agonist-stimulated inositol polyphosphate production was investigated in slices of rat cerebral cortex. LiCl potentiated the formation of inositol monophosphate and inositol bisphosphate following stimulation with a variety of agonists including carbachol (1 mM), noradrenaline (NA, 300 ?M), 5-hydroxytryptamine (5-HT, 100 ?M) and quisqualic acid (Quis, 100 ?M), the EC(50) for these effects was in the range 0.5-5 mM. The production of inositol trisphosphate and inositol tetrakisphosphate following NA, 5-HT or Quis stimulation was not significantly affected by LiCl, though there was a delayed but striking inhibition of both the inositol 1,4,5-trisphosphate and, particularly, inositol tetrakisphosphate responses to carbachol, which was even greater in buffer containing elevated (20 mM) KCl. The possible mechanisms underlying this effect of LiCl are discussed in relation to previously observed effects of this ion on phosphoinositide metabolism.
Godfrey
P P
PP
MRC Unit and University Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, England.
Taghavi
Z
Z
Parfrey
H
H
Grahame-Smith
D G
DG