title: Influences of cholecystokinin octapeptide on phosphoinositide turnover in neonatal-rat brain cells.
abstract: Cholecystokinin octapeptide (CCK-8) has been shown to be coupled to phosphoinositide turnover in pancreatic acini as well as in a kind of neuroblastoma cell and a human embryonic cell line. Little is known, however, about its link with phosphatidylinositol breakdown in the brain. The brains (minus cerebella) from 1-2-day-old neonatal rats were enzymically dissociated into single cells. The intact cells were prelabelled by incubation with myo-[3H]inositol for 3 h, and were then stimulated with agonists in the presence of 10 mM-LiCl. Carbachol at 1 mM induced an increase in InsP3 labelling in brain cells (peak at 30 min, and then a gradual decrease), and a static accumulation of InsP with time, whereas the labelling of InsP2 remained essentially unchanged. A very similar time-response curve was obtained for 10 nM-CCK-8 in stimulating phosphoinositide turnover. The dose-response curve for incubated brain cells revealed that the formation of InsP3 increased when the concentration of CCK-8 was increased from 0.1 to 10 nM. A further increase in CCK-8 concentration to 100-1000 nM resulted in a gradual decrease in InsP3 formation. InsP and InsP2 levels stayed relatively stable. The production of InsP3 stimulated by 10 nM-CCK-8 was dose-dependently suppressed by the CCK-A antagonist Devazepide in the concentration range 1-10 nM; the effect declined when the concentration was further increased to 100-1000 nM. In contrast, the CCK-B antagonist L365,260 showed a sustained suppression of InsP3 production at concentrations above 0.1 nM, i.e. in the range 1-1000 nM. The results provide evidence that CCK-8 stimulates the turnover of phosphoinositide and increases InsP3 labelling in dissociated neonatal-rat brain cells, in which both CCK-A and CCK-B receptors seem to be involved.
authors.affiliation: Neuroscience Research Center, Beijing Medical University, People's Republic of China.
authors.forename: L J
authors.initials: LJ
authors.lastname: Zhang
authors.forename: X Y
authors.initials: XY
authors.lastname: Lu
authors.forename: J S
authors.initials: JS
authors.lastname: Han
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001570:Benzodiazepinones / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D020109:Devazepide; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D010671:Phenylurea Compounds; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D001570:Benzodiazepinones; D002712:Chlorides; D010671:Phenylurea Compounds; D010716:Phosphatidylinositols; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002217:Carbachol; D008094:Lithium; D018021:Lithium Chloride; D020109:Devazepide; D012844:Sincalide