Muscarinic receptor-linked elevation of cAMP in SH-SY5Y neuroblastoma cells is mediated by Ca2+ and protein kinase C.
The mechanisms of muscarinic receptor-linked increase in cAMP accumulation in SH-SY5Y human neuroblastoma cells has been investigated. The dose-response relations of carbachol-induced cAMP synthesis and carbachol-induced rise in intracellular free Ca2+ were similar. The stimulated cAMP synthesis was inhibited by about 50% when cells were entrapped with the Ca2+ chelator BAPTA or in the presence of the protein kinase C (PKC) inhibitor staurosporine. Production of cAMP could be induced also by the Ca2+ ionophore, ionomycin and by TPA, an activator of PKC. When added together TPA and ionomycin had a synergistic effect. When cAMP synthesis was activated with cholera toxin, PGE1 or PGE1 + pertussis toxin carbachol stimulated cAMP production to the same extent as in control cells. Ca2+ and protein kinase C thus seem to be the mediators of muscarinic-receptor linked cAMP synthesis by a direct action on adenylate cyclase.
Jansson
C C
CC
Department of Biochemistry and Pharmacy, Abo Akademi, Finland.
Kukkonen
J
J
Akerman
K E
KE
D037361:Adenylate Cyclase Toxin; D000527:Alprostadil / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D009447:Neuroblastoma / Q000378:metabolism*; D037342:Pertussis Toxin; D010890:Pirenzepine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D015290:Second Messenger Systems; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D010890:Pirenzepine; D002217:Carbachol; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D000527:Alprostadil; D002118:Calcium