Area specific alterations in muscarinic stimulated low Km GTPase activity in aging and Alzheimer's disease: implications for altered signal transduction.
Carbachol-stimulated low Km GTPase activity (an index of muscarinic receptor-G protein coupling) was examined in hippocampus, basal ganglia, orbital frontal gyrus and superior frontal gyrus obtained from mature, aged and Alzheimer's Disease (AD) groups. Results indicated that carbachol-stimulated low Km GTPase activities in basal ganglia were as follows: mature controls > aged > AD, and there was a trend toward a similar pattern of decline in the hippocampus. No differences were seen in the two cortical areas examined; however, carbachol-stimulated low Km GTPase activity was small in the mature controls. Importantly, there were significant negative correlations between disease duration and carbachol-stimulated low Km GTPase activity in all areas examined except the orbital frontal gyrus. The longer the duration of the disease the lower the carbachol-stimulated low Km GTPase activity. Results suggest that age and disease-related changes in mAChR-G protein interactions in the basal ganglia may contribute to reduced signal transduction (ST). In addition, since decreased carbachol-stimulated low Km GTPase activity has also been observed in the aged rat; thus, investigations of the factors involved in decrements in signal transduction in the aged rat may be useful for understanding these alterations in aged humans or victims of AD.
Cutler
R
R
Molecular Physiology and Genetics Section, Gerontology Research Center, Baltimore, MD 21224.
Joseph
J A
JA
Yamagami
K
K
Villalobos-Molina
R
R
Roth
G S
GS
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000201:enzymology*; D002217:Carbachol / Q000494:pharmacology*; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D011976:Receptors, Muscarinic / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013268:Stimulation, Chemical
D011976:Receptors, Muscarinic; D002217:Carbachol; D020558:GTP Phosphohydrolases