AREA-SPECIFIC ALTERATIONS IN MUSCARINIC STIMULATED LOW K-M GTPASE ACTIVITY IN AGING AND ALZHEIMERS-DISEASE - IMPLICATIONS FOR ALTERED SIGNAL-TRANSDUCTION

Carbachol-stimulated low K-m 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 K-m 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 K-m GTPase activity was small in the mature controls. Importantly, there were significant negative correlations between disease duration and carbachol-stimulated low K-m GTPase activity in all areas examined except the orbital frontal gyrus. The longer the duration of the disease the lower the carbachol-stimulated low K-m 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 K-m 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.