Decrement of muscarinic receptor-stimulated low-KM GTPase in striatum and hippocampus from the aged rat.
Previous studies have shown that there is an age-related loss of responsiveness in several different receptor systems (e.g. beta-adrenergic, dopaminergic and muscarinic). Our research, using perifused striatal slices and examining muscarinic agonist enhancement of K(+)-evoked dopamine release, has determined that at least part of the loss of sensitivity in muscarinic receptors (mAChR) may occur early in the post-receptor signal transduction process. The present study was carried out to further characterize and localize this deficit by examining carbachol- and oxotremorine-stimulated low-KM guanosine triphosphatase (GTPase) activity in striatal as well as hippocampal tissue obtained from adult (6 months) and old (24 months) Wistar rats. Receptor stimulated low-KM GTPase catalyzes the conversion of GTP to GDP to end the signal transduction cycle and is an indicator of receptor-G-protein coupling/uncoupling. The results showed that stimulated GTPase activity was significantly reduced in hippocampal and striatal tissue from the old animals. These findings suggest that there may be an age-related coupling/uncoupling deficit between muscarinic receptor and G-proteins, and that this deficit may contribute to the reduced mAChR responsiveness in senescence.
Yamagami
K
K
Molecular Physiology and Genetics Section, NIA, Francis Scott Key Medical Center, Baltimore, MD 21224.
Joseph
J A
JA
Roth
G S
GS
D000375:Aging; D000818:Animals; D015153:Blotting, Western; D002217:Carbachol / Q000494:pharmacology*; D002462:Cell Membrane / Q000201:enzymology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D007700:Kinetics; D046911:Macromolecular Substances; D008297:Male; D008970:Molecular Weight; D010095:Oxotremorine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D046911:Macromolecular Substances; D011976:Receptors, Muscarinic; D010095:Oxotremorine; D002217:Carbachol; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins