Potassium depolarisation markedly enhances muscarinic receptor stimulated inositol tetrakisphosphate accumulation in rat cerebral cortical slices.
Rat cerebral cortical slices labelled with [3H]-inositol were incubated with the muscarinic agonist carbachol in media containing normal 5.9 mM or elevated 24 mM K+ ions. Over the first few minutes both carbachol and elevated K+ stimulated the production of [3H]-inositol phosphates. The very rapid formation of [3H]-inositol tetrakis, tris and bisphosphate was followed by accumulation of [3H]-inositol monophosphate. However, elevated K+ resulted in a relatively larger stimulation of [3H]-inositol bisphosphate than muscarinic receptor stimulation. When carbachol effects were examined in media containing elevated K+, production of [3H]-inositol trisphosphate was apparently additive whereas the mono and bisphosphate displayed somewhat synergistic responses after 1-2 minutes. In contrast, [3H]-inositol tetrakisphosphate production was greatly enhanced and marked synergy was observed between the K+ and carbachol responses. The production of the tetrakisphosphate under these conditions was dependent on extracellular Ca2+ and a stimulatory effect of this divalent ion on the 3-kinase is discussed.
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008297:Male; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000502:physiology*; D013403:Sugar Phosphates / Q000096:biosynthesis*
D007295:Inositol Phosphates; D011976:Receptors, Muscarinic; D013403:Sugar Phosphates; D002217:Carbachol; D011188:Potassium