Summary
The metabolism of phosphoinositides that results from receptor-coupled processes in the CNS can be readily detected in rats treated with low doses of lithium chloride. Brain levels of myo-inositol 1-phosphate (IP) rise in response to agonists of this class of receptor and decrease on treatment with antagonists. For example, peripheral administration of the direct-acting muscarinic cholinergic agonist pilocarpine causes a rapid (<30 min) increase in the IP levels of cerebral cortex. Subsequent administration of the muscarinic antagonist atropine reverses the effect. The anticholinesterase physostigmine produces a similar IP elevation. Both of these agents produce seizures when given to lithium-treated rats. Because diazepam reduces the increase in IP while arresting seizures and because peripherally-administered kainic acid causes both seizures and an elevation in IP level that is partially reversed by atropine, we believe that the seizure activity itself contributes to the increase in IP observed. Nicotine, when administered subcutaneously to the lithium-treated rat, suppresses IP levels, while the two nicotinic cholinergic ganglionic blockers mecamylamine and pempidine give rise to atropine-reversible increases in IP that are comparable to the increases obtained with muscarinic agonists but without producing seizures. The effect of the nicotinic blockers is ascribed to disinhibition of Renshaw cell-like circuits.
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Sherman, W.R., Honchar, M.P., Munsell, L.Y. (1985). Detection of Receptor-Linked Phosphoinositide Metabolism in Brain of Lithium-Treated Rats. In: Bleasdale, J.E., Eichberg, J., Hauser, G. (eds) Inositol and Phosphoinositides. Experimental Biology and Medicine, vol 6. Humana Press. https://doi.org/10.1007/978-1-4612-5184-2_4
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DOI: https://doi.org/10.1007/978-1-4612-5184-2_4
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