Depolarisation-evoked release of acetylcholine can mediate phosphoinositide hydrolysis in slices of rat cerebral cortex.
Depolarisation of [3H]inositol prelabelled slices of cerebral cortex of the rat, with elevated extracellular K+ or the alkaloid veratrine, induced a marked accumulation of [3H]inositol monophosphate in the presence of 5 mM Li+. The effects of these stimuli were concentration-related with maximal responses obtained at 30 mM K+ and 30 microM veratrine. Larger concentrations produced submaximal responses but also markedly suppressed the incorporation of [3H]inositol into phospholipid. The responses to K+ or veratrine were not sensitive to atropine, prazosin, mepyramine, ketanserin or the peptidase inhibitor bacitracin. However, in the presence of the cholinesterase inhibitor physostigmine, the responses to these stimuli were greatly enhanced and this could be blocked by atropine. Both veratrine and K+ markedly stimulate release of endogenous acetylcholine from the slices. Release appears to be linear with time over the 45 min period of continuous stimulation. Reduction of extracellular calcium severely suppressed both the release of acetylcholine and the atropine-sensitive component of the phosphoinositide response to K+. The results suggest that endogenous acetylcholine can stimulate phosphoinositide metabolism by interacting with muscarinic receptors. The atropine-insensitive component, at least in part, represents entry of Ca2+ through voltage-sensitive channels and perhaps a direct effect on phosphoinositide metabolism.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D010716:Phosphatidylinositols / Q000378:metabolism*; D010830:Physostigmine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000502:physiology*; D014702:Veratrine / Q000494:pharmacology
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D001285:Atropine; D002217:Carbachol; D010830:Physostigmine; D014702:Veratrine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium