Dual effects of K+ depolarisation on inositol polyphosphate production in rat cerebral cortex.
Depolarisation of [3H]inositol-prelabelled slices of rat cerebral cortex with elevated extracellular K+ induced a rapid and marked increase in inositol polyphosphate accumulation. Addition of the muscarinic antagonist atropine (10 microM) markedly inhibited the K+-induced accumulation of inositol tetrakisphosphate (InsP4), with only a slight reduction in stimulated inositol bis- and trisphosphate levels. Inhibitory effects on InsP4 were noted at the earliest time period measured (30 s) and suggested the involvement of released endogenous acetylcholine in part of the response. The atropine-insensitive component of depolarisation did not appear to be secondary to release of noradrenaline, histamine, or 5-hydroxytryptamine, because addition of prazosin, mepyramine, or ketanserin was without effect on the K+ response. Furthermore, secretion of a neuropeptide that could stimulate phosphoinositide hydrolysis was unlikely, because the peptidase inhibitor bacitracin was also without effect. The results suggest that endogenous acetylcholine can stimulate phosphoinositide metabolism by interacting with muscarinic receptors and that this is particularly evident on InsP4 accumulation. Atropine-insensitive responses may be secondary to Ca2+ entry via voltage-sensitive channels.
Baird
J G
JG
Department of Pharmacology and Therapeutics, University of Leicester, England.
Nahorski
S R
SR
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001414:Bacitracin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D013403:Sugar Phosphates / Q000378:metabolism*
D007295:Inositol Phosphates; D013403:Sugar Phosphates; D001414:Bacitracin; D001285:Atropine; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D000109:Acetylcholine; D011188:Potassium