Modulation by GM1 ganglioside of beta 1-adrenergic receptor-induced cyclic AMP formation in Sf9 cells.
The effect of ganglioside GM1 on isoproterenol-induced cAMP accumulation was studied in insect Sf9 cells expressing the human beta 1-adrenergic receptor by infection with recombinant baculovirus. When such Sf9 cells were treated with isoproterenol plus IBMX, intracellular cAMP formation increased approximately 10-fold over the basal level. Preincubation of the baculovirus-infected cells with GM1 for 1 h caused a concentration-dependent inhibition of the isoproterenol-induced cAMP accumulation. Phosphatidylserine, GM3, GT1b and a bovine brain ganglioside preparation lacking GM1 did not cause significant inhibition. Forskolin-induced cAMP accumulation was not affected by the GM1 treatment. Inhibition of isoproterenol-induced cAMP formation by GM1 was not observed in Sf9 cells expressing beta 2-adrenergic receptor instead of the beta 1-adrenergic receptor. Binding studies with (-)-[3H]CGP12177 showed that preincubation with GM1 significantly reduced the affinity of antagonist binding to the beta 1-adrenergic receptor. These results suggest that GM1 or related ganglioside structure(s) may function as natural modulator(s) of the beta 1-adrenergic receptor.
Saito
M
M
New Jersey Medical School, UMDNJ, Department of Neurosciences, Newark 07103, USA.
Frielle
T
T
Benovic
J L
JL
Ledeen
R W
RW
D000249:Adenosine Monophosphate / Q000096:biosynthesis*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D016367:Baculoviridae / Q000378:metabolism; D002460:Cell Line; D005677:G(M1) Ganglioside / Q000378:metabolism*; D006801:Humans; D007313:Insecta; D007545:Isoproterenol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D005677:G(M1) Ganglioside; D000249:Adenosine Monophosphate; D007545:Isoproterenol; C033394:CGP 12177