Effects of CDP-choline administration on receptor-stimulated inositol phospholipid hydrolysis in brain slices and neuronal cultures.
Repeated addition of CDP-choline (100 microM, once a day since the 2nd day of maturation in culture) to corticostriatal neurons led to an increased basal hydrolysis of inositol phospholipids, as revealed by an enhanced formation of [3H]inositolmonophosphate ([3H]InsP) in the presence of 10 mM Li+. This increase was prevented by the muscarinic receptor antagonist, atropine, or by tetrodotoxin, but not by other receptor antagonists, such as L-2-amino-4-phosphonobutanoate (L-AP4), prazosin or ketanserin. The increase in inositol phospholipid hydrolysis induced by repeated addition of CDP-choline was obliterated when cultures were incubated in the presence of the muscarinic receptor agonist, carbamylcholine. CDP-choline had no effect on inositol phospholipid hydrolysis in cultured cerebellar neurons, which are devoid of cholinergic cells. The basal hydrolysis of inositol phospholipids was also increased in hippocampal slices prepared from rats repeatedly injected with CDP-choline (200 mg/kg, i.p. for 15 days). As observed in cultured cortico-striatal neurons, this increase was prevented by atropine and was masked in the presence of carabamylcholine. Taken collectively, these data indicate that repeated exposure to exogenous CDP-choline increases polyphosphoinositide turnover, an effect that results from an increased availability of acetylcholine acting on muscarinic receptors.
Canonico
P L
PL
Institute of Pharmacology, University of Catania School of Medicine, Italy.
Nicoletti
F
F
Sortino
M A
MA
Aleppo
G
G
Scapagnini
U
U
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D046508:Culture Techniques; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D006868:Hydrolysis; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D003566:Cytidine Diphosphate Choline; D000109:Acetylcholine