G蛋白
内分泌学
内科学
百日咳毒素
腺苷酸环化酶
受体
兴奋剂
毒蕈碱乙酰胆碱受体
生物
化学
分子生物学
医学
作者
Meisheng Jiang,Michael H. Gold,Guylain Boulay,Karsten Spicher,Michael Peyton,Philippe Brabet,Yogambul Srinivasan,Uwe Rudolph,Gaylord Ellison,Lutz Birnbaumer
标识
DOI:10.1073/pnas.95.6.3269
摘要
The G protein G o is highly expressed in neurons and mediates effects of a group of rhodopsin-like receptors that includes the opioid, α 2 -adrenergic, M2 muscarinic, and somatostatin receptors. In vitro , G o is also activated by growth cone-associated protein of M r 43,000 (GAP43) and the Alzheimer amyloid precursor protein, but it is not known whether this occurs in intact cells. To learn about the roles that G o may play in intact cells and whole body homeostasis, we disrupted the gene encoding the α subunits of G o in embryonic stem cells and derived G o -deficient mice. Mice with a disrupted α o gene (α o −/− mice) lived but had an average half-life of only about 7 weeks. No G o α was detectable in homogenates of α o −/− mice by ADP-ribosylation with pertussis toxin. At the cellular level, inhibition of cardiac adenylyl cyclase by carbachol (50–55% at saturation) was unaffected, but inhibition of Ca 2+ channel currents by opioid receptor agonist in dorsal root ganglion cells was decreased by 30%, and in 25% of the α o −/− cells examined, the Ca 2+ channel was activated at voltages that were 13.3 ± 1.7 mV lower than in their counterparts. Loss of α o was not accompanied by appearance of significant amounts of active free βγ dimers (prepulse test). At the level of the living animal, G o -deficient mice are hyperalgesic (hot-plate test) and display a severe motor control impairment (falling from rotarods and 1-inch wide beams). In spite of this deficiency, α o −/− mice are hyperactive and exhibit a turning behavior that has them running in circles for hours on end, both in cages and in open-field tests. Except for one, all α o −/− mice turned only counterclockwise. These findings indicate that G o plays a major role in motor control, in motor behavior, and in pain perception and also predict involvement of G o in Ca 2+ channel regulation by an unknown mechanism.
科研通智能强力驱动
Strongly Powered by AbleSci AI