Pertussis toxin inhibits alpha 2-adrenoceptor-mediated inhibition of adenylate cyclase without affecting muscarinic regulation of [Ca2+]i or inositol phosphate generation in SH-SY5Y human neuroblastoma cells.
The present study reports the differential effects of pertussis toxin on muscarinic regulation of intracellular Ca2+ and inositol phosphate generation and alpha 2-adrenoceptor-mediated inhibition of cAMP formation in SH-SY5Y human neuroblastoma cells. Carbachol caused a biphasic increase in intracellular Ca2+ (release of internal stores and Ca2+ entry) and a dose-dependent increase in inositol phosphate formation. Pertussis toxin pretreatment did not affect either of these components of the signal transduction pathway but did completely reverse the alpha 2-adrenoceptor-mediated inhibition of forskolin-stimulated cAMP formation. These data indicate that muscarinic regulation of inositol phosphate generation occurs via a pertussis toxin-insensitive G-protein and that Ca2+ entry in these cells may not occur via a G-protein.
Lambert
D G
DG
Department of Pharmacology and Therapeutics, University of Leicester, U.K.
Nahorski
S R
SR
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism; D037342:Pertussis Toxin; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D002118:Calcium