Potassium ions potentiate the muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortex slices: A comparison of neonatal and adult rats
Autor: | Lucio G. Costa, Walter Balduini, Sheldon D. Murphy |
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Rok vydání: | 1990 |
Předmět: |
Male
Aging medicine.medical_specialty Carbachol Stimulation Biology Phosphatidylinositols Biochemistry Norepinephrine Cellular and Molecular Neuroscience chemistry.chemical_compound Internal medicine Muscarinic acetylcholine receptor medicine Animals Inositol Channel blocker Cerebral Cortex Tetraethylammonium General Medicine Muscarinic acetylcholine receptor M1 Receptors Muscarinic Rats Endocrinology Animals Newborn chemistry Potassium Cholinergic Female medicine.drug |
Zdroj: | Neurochemical Research. 15:33-39 |
ISSN: | 1573-6903 0364-3190 |
DOI: | 10.1007/bf00969181 |
Popis: | Activation of cholinergic muscarinic receptors results in an increased turnover of membrane inositol phospholipids. In rat cerebral cortex slices, carbachol- and acetylcholine-induced inositol phosphates ([3H]InsPs) accumulation is maximal in 7 day-old rats and lowest in adults, while the density of muscarinic binding sites increases gradually with age, suggesting the presence of a more effective receptor-effector coupling during neonatal life. In the process of investigating the nature of such differential stimulation, we have studied the effects of potassium ions on muscarinic receptor-stimulated phosphoinositide metabolism during development. Increasing the concentration of K+ from 6 to 12 mM potentiated the stimulating effect of carbachol by 80–100% in adult animals, as previously shown, but only 10–20% in 7 day-old animals, without altering its EC50 values. The differential potentiation by K+ at these two ages was specific for muscarinic receptors, since norepinephrine-stimulated accumulation was potentiated only 18% and 12% in adult and 7 day-old rats, respectively. Two other monovalent cations, rubidium and cesium, had the same effect as K+ on carbachol-stimulated [3H]-InsPs accumulation. The effect of K+ was not antagonized by the K+ channel blocker 4-aminopyridine, but was antagonized by tetraethylammonium (TEA). TEA, however, also interacted with muscarinic binding sites. Omission of calcium from the incubation medium did not influence the potentiating effect of 12 mM K+. However, when EDTA (1 mM) was added, the stimulating effect of carbachol alone or carbachol + K+ was almost completely prevented. The potentiating effect of K+ during development was inversely proportional to the stimulation of phosphoinositide metabolism induced by carbachol. These results suggest that the mechanism responsible for the potentiating effect of K+ in adult rats might be already operating in neonatal animals. |
Databáze: | OpenAIRE |
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