Potassium ion facilitation of phosphoinositide turnover activation by muscarinic receptor agonists in rat brain.
In rat hippocampal slices kept in Krebs-Henseleit medium, an increase of K+ ions to 12 mM potentiates the stimulation of phosphoinositide turnover elicited by carbachol and (+/-)-cis-methyldioxolane. Oxotremorine is inactive if tested in Krebs-Henseleit medium but it stimulates by 220% the phosphoinositide turnover when K+ is increased to 12 mM. The K+ facilitation of the carbachol stimulation of phosphoinositide turnover was blocked by pirenzepine, a muscarinic antagonist. This drug was equally potent in inhibiting the carbachol stimulation of phosphoinositide turnover both in normal and 12 mM K+ Krebs medium. This facilitatory effect of K+ appears to be preferential for muscarinic receptors, since it failed to increase the activation of phosphoinositide breakdown induced by norepinephrine and histamine. The K+ potentiation of the muscarinic stimulation of phosphoinositide turnover is not mediated by a release of one of the endogenous neurotransmitters stored in these slices because such a facilitation occurs in Ca2+-deprived Krebs-Henseleit medium and failed to occur following a depolarizing dose of veratrine. Our experiments excluded that K+ facilitates carbachol stimulation of phosphoinositide turnover because it modifies the binding characteristics of muscarinic receptors; however, they cannot exclude that K+ acts at the receptor transducer coupling.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004148:Dioxolanes / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010890:Pirenzepine; D011188:Potassium / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D001570:Benzodiazepinones; D004148:Dioxolanes; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D010890:Pirenzepine; C024310:2-methyldioxolane; D010095:Oxotremorine; D006632:Histamine; D002217:Carbachol; D011188:Potassium; D009638:Norepinephrine