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
Rok vydání: 1990
Předmět:
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