Saito M, Frielle T, Benovic J L, Ledeen R W
New Jersey Medical School, UMDNJ, Department of Neurosciences, Newark 07103, USA.
Biochim Biophys Acta. 1995 May 29;1267(1):1-5. doi: 10.1016/0167-4889(95)00026-o.
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.
通过重组杆状病毒感染，在表达人β1 - 肾上腺素能受体的昆虫Sf9细胞中研究了神经节苷脂GM1对异丙肾上腺素诱导的环磷酸腺苷（cAMP）积累的影响。当用异丙肾上腺素加异丁基甲基黄嘌呤（IBMX）处理这种Sf9细胞时，细胞内cAMP的形成比基础水平增加了约10倍。用GM1将杆状病毒感染的细胞预孵育1小时会导致异丙肾上腺素诱导的cAMP积累呈浓度依赖性抑制。磷脂酰丝氨酸、GM3、GT1b和一种不含GM1的牛脑神经节苷脂制剂未引起明显抑制。佛司可林诱导的cAMP积累不受GM1处理的影响。在表达β2 - 肾上腺素能受体而非β1 - 肾上腺素能受体的Sf9细胞中未观察到GM1对异丙肾上腺素诱导的cAMP形成的抑制作用。用（ - ） - [3H]CGP12177进行的结合研究表明，用GM1预孵育会显著降低拮抗剂与β1 - 肾上腺素能受体结合的亲和力。这些结果表明，GM1或相关神经节苷脂结构可能作为β1 - 肾上腺素能受体的天然调节剂发挥作用。
