Altered phosphoinositide-specific phospholipase C and adenylyl cyclase in brain cortical membranes of cats with GM1 and GM2 gangliosidosis.
Phosphoinositide-specific phospholipase C and adenylyl cyclase were studied in brain cortical membranes from cats with GM1 and GM2 gangliosidosis. In contrast to brain cortical membranes from unaffected control cats, phospholipase C acting against exogenously supplied phosphoinositide substrates did not respond to stimulation by GTP gamma S, carbachol or fluoroaluminate in cortical membranes of cats with gangliosidosis. However, the enzyme was activated by calcium in membranes from affected cats to the same extent as in membranes from control cats. Basal adenylyl cyclase activity was increased 3-fold in cortical membranes of cats with GM1 and GM2 gangliosidosis, compared with unaffected sibling controls. Fluoroaluminate was equally effective in stimulating adenylyl cyclase in controls and in membranes of affected and normal cats. In addition, GppNHp was able to inhibit the forskolin-activated enzyme both in membranes from cats with gangliosidosis and sibling controls. These data suggest that the activation of phosphoinositide-specific phospholipase C in brain membranes by guanine nucleotide binding proteins is markedly impaired in GM1 and GM2 gangliosidoses.
Claro
E
E
Department of Biochemistry, University of Tennessee, Memphis 38163.
Wallace
M A
MA
Fain
J N
JN
Nair
B G
BG
Patel
T B
TB
Shanker
G
G
Baker
H J
HJ
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000535:Aluminum / Q000494:pharmacology; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002371:Cat Diseases / Q000201:enzymology*; D002415:Cats; D002462:Cell Membrane / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology*; D002712:Chlorides / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000378:metabolism*; D005733:Gangliosidoses / Q000201:enzymology* / Q000662:veterinary*; D016537:Gangliosidosis, GM1 / Q000201:enzymology* / Q000662:veterinary*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007700:Kinetics; D019269:Phosphatidylinositol 4,5-Diphosphate; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D012016:Reference Values; D012969:Sodium Fluoride / Q000494:pharmacology
D017607:Aluminum Compounds; D002712:Chlorides; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D005677:G(M1) Ganglioside; D000077410:Aluminum Chloride; D002217:Carbachol; D012969:Sodium Fluoride; D000535:Aluminum; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D002118:Calcium