Carbachol- and KCl-induced changes in phosphoinositide metabolism and free calcium in guinea pig cerebral cortex synaptosomes.
Phosphoinositide (PI) and calcium metabolism were studied in guinea pig cerebral cortex synaptosomes. Mass amounts of inositol and inositol monophosphates, and the levels of free intrasynaptosomal calcium ([Ca2+]i) were measured after KCl (60 mM), after a direct cholinergic agonist carbachol (CA, 1mM), and after their combination. Inositol, inositol-1-phosphate (Ins1P), inositol-4-phosphate (Ins4P) and [Ca2+]i were measured with and without 10 mM LiCl in the incubation medium. CA-induced cholinergic stimulation elevated synaptosomal Ins4P levels by 40% but did not affect Ins1P or [Ca2+]i. On the contrary, KCl elevated Ins1P by 50% and [Ca2+]i by 40% above the resting level, and decreased inositol by 20%, whereas no alterations in Ins4P occurred. CA did not modify the responses of KCl, but KCl abolished the elevation of Ins4P by CA. LiCl attenuated KCl-induced elevation of Ins1P but amplified the CA-induced elevation of Ins4P. The elevation of presynaptic [Ca2+]i was accompanied by accumulation of Ins1P but not that of Ins4P. Hence, the present results suggest that presynaptic cholinergic stimulation and KCl-induced depolarization may activate different degradation pathways of inositolphosphate metabolism.
Division of Environmental Health, National Public Health Institute, Kuopio, Finland.
M R
MR
Hirvonen
H
H
Komulainen
K
K
Savolainen
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007295:Inositol Phosphates / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002712:Chlorides; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; C002647:inositol 1-phosphate; C045537:inositol 4-phosphate; D011189:Potassium Chloride; D002217:Carbachol; D008094:Lithium; D018021:Lithium Chloride; D002118:Calcium