Potassium ions potentiate the muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortex slices: a comparison of neonatal and adult rats.
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 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.
Balduini
W
W
Department of Environmental Health, University of Washington, Seattle 98195.
Costa
L G
LG
Murphy
S D
SD
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D002217:Carbachol; D011188:Potassium; D009638:Norepinephrine