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 r eceptor-G protein coupling) was examined in hippocampus, basal ganglia , orbital frontal gyrus and superior frontal gyrus obtained from matur e, aged and Alzheimer's Disease (AD) groups. Results indicated that ca rbachol-stimulated low K-m GTPase activities in basal ganglia were as follows: mature controls > aged > AD, and there was a trend toward a s imilar 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, th ere were significant negative correlations between disease duration an d carbachol-stimulated low K-m GTPase activity in all areas examined e xcept the orbital frontal gyrus. The longer the duration of the diseas e the lower the carbachol-stimulated low K-m GTPase activity. Results suggest that age and disease-related changes in mAChR-G protein intera ctions in the basal ganglia may contribute to reduced signal transduct ion (ST). In addition, since decreased carbachol-stimulated low K-m GT Pase activity has also been observed in the aged rat; thus, investigat ions of the factors involved in decrements in signal transduction in t he aged rat may be useful for understanding these alterations in aged humans or victims of AD.