A rapid attenuation of muscarinic agonist stimulated phosphoinositide hydrolysis precedes receptor sequestration in human SH-SY-5Y neuroblastoma cells.
Agonist occupancy of muscarinic cholinergic receptors in human SH-SY-5Y neuroblastoma cells elicited two kinetically distinct phases of phosphoinositide hydrolysis when monitored by either an increased mass of inositol 1,4,5-trisphosphate, or the accumulation of a total inositol phosphate fraction. Within 5s of the addition of the muscarinic agonist, oxotremorine-M, the phosphoinositide pool was hydrolyzed at a maximal rate of 9.5%/min. This initial phase of phosphoinositide hydrolysis was short-lived (t1/2 = 14s) and after 60s of agonist exposure, the rate of inositol lipid breakdown had declined to a steady state level of 3.4%/min which was then maintained for at least 5-10 min. This rapid, but partial, attenuation of muscarinic receptor stimulated phosphoinositide hydrolysis occurred prior to the agonist-induced internalization of muscarinic receptors.
Fisher
S K
SK
Department of Pharmacology, University of Michigan Ann Arbor 48104-1687.
Slowiejko
D M
DM
McEwen
E L
EL
D005591:Chemical Fractionation; D006801:Humans; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate / Q000737:chemistry; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D015544:Inositol 1,4,5-Trisphosphate