Abstract

Cholinergic and adrenergic neurotransmission in brain is mediated in part through muscarinic and alpha-1-adrenergic receptor stimulated phosphoinositide hydrolysis. A variety of evidence suggests that cholinergic and adrenergic neurotransmission is disrupted during aging. The loss of cognitive function which occurs during normal aging, senile dementia and Alzheimer's disease is likely to be related to change in cholinergic neurotransmission during aging. The administration of muscarinic cholinergic antagonists produces memory deficits in young animals similar to those found to occur naturally in aged animals. An understanding of muscarinic cholinergic and alpha 1- adrenergic receptor stimulated phosphoinositide hydrolysis is essential for a complete understanding of the mechanisms of cholinergic and adrenergic transmission in brain. The long-term objective of this proposal is to determine the properties and mechanisms of adrenergic and cholinergic receptor coupling to phosphoinositide hydrolysis in brain and how these processes are altered during senescence.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG006660-02
Application #
3117792
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1987-09-30
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Kurian, P; Chandler, L J; Patel, R et al. (1992) Receptor coupling to phosphoinositide signals. Adv Exp Med Biol 318:399-411
Kurian, P; Narang, N; Crews, F T (1992) Decreased carbachol-stimulated inositol 1,3,4,5-tetrakisphosphate formation in senescent rat cerebral cortical slices. Neurobiol Aging 13:521-6
Narang, N; Garg, L C; Crews, F T (1990) Adenosine and its analogs stimulate phosphoinositide hydrolysis in the kidney. Pharmacology 40:90-5
Pontzer, N J; Chandler, L J; Stevens, B R et al. (1990) Receptors, phosphoinositol hydrolysis and plasticity of nerve cells. Prog Brain Res 86:221-5
Pontzer, N J; Crews, F T (1990) Desensitization of muscarinic stimulated hippocampal cell firing is related to phosphoinositide hydrolysis and inhibited by lithium. J Pharmacol Exp Ther 253:921-9
Chandler, L J; Crews, F T (1989) Calcium- versus G-protein-activated phosphoinositide hydrolysis in synaptoneurosomes from young and old rats. Ann N Y Acad Sci 568:187-92