Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptor is believed to be central to synaptic plasticity in the mammalian brain. It is implicated in epilepsy and excitoxicity. Thus the mechanisms and factors which modulate AMPA receptor activity are of considerable interest. The focus of this project is to determine the functional properties of AMPA receptors and associated ion channels by the use of compounds which modulate receptor function. The long-term objective is to uncover the role of AMPA receptors in synaptic plasticity and long term potentiation (LTP). LTP is a form of synaptic plasticity thought to underlie learning and memory. It is noted that during the purification process heparin bound with high affinity to solubilized AMPA receptors and altered their channel kinetics. The effects of heparin and other glycosaminoglycans (GAGs) on single channel kinetics of purified and reconstituted AMPA receptors will be determined. Biochemical studies indicated that heparin has little effect on membrane associated AMPA receptors. During reconstruction experiments heparin and dextran sulfate induced AMPA channels of very high conductivity. Thus this project will define the mechanism responsible for the differences in responses of membrane associated and solubilized receptors to glycosaminoglycans. This will be achieved by electrophysiological analysis of reconstituted. This will be achieved by electrophysiological analysis of reconstituted crude synaptic preparations that have been treated with specific enzymes to remove glycosaminoglycans. This project will also investigate the role of glycosaminoglycans on the increase cooperativity among AMPA receptor channels and the effects of centrally active drugs (benzoyl pyridine derivatives) on AMPA receptors and associated channels. These drugs have been shown to result in substantial improvement in retention scores of rats and human subjects tested on various memory tasks, possibly due to modulation of AMP receptors and associated ion channels.

Project Start
2000-06-01
Project End
2001-05-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
29
Fiscal Year
2000
Total Cost
$30,384
Indirect Cost
Name
Tuskegee University
Department
Type
DUNS #
128214178
City
Tuskegee
State
AL
Country
United States
Zip Code
36088
Mathews, Ensa; Braden, Tim D; Williams, Carol S et al. (2009) Mal-development of the penis and loss of fertility in male rats treated neonatally with female contraceptive 17alpha-ethinyl estradiol: a dose-response study and a comparative study with a known estrogenic teratogen diethylstilbestrol. Toxicol Sci 112:331-43
Goyal, H O; Braden, T D; Williams, C S et al. (2009) Estrogen-induced developmental disorders of the rat penis involve both estrogen receptor (ESR)- and androgen receptor (AR)-mediated pathways. Biol Reprod 81:507-16
Cooper, Marvis S; Reeve Jr, Joseph R; Abdalla, Mohamed O et al. (2008) Cholecystokinin-33 is more effective than cholecystokinin-8 in inhibiting food intake and in stimulating the myenteric plexus and dorsal vagal complex. Brain Res 1205:27-35
Raboin, Shannon J; Reeve Jr, Joseph R; Cooper, Marvis S et al. (2008) Activation of submucosal but not myenteric plexus of the gastrointestinal tract accompanies reduction of food intake by camostat. Regul Pept 150:73-80
Cooper, Marvis S; Reeve Jr, Joseph R; Raboin, Shannon J et al. (2008) Cholecystokinin-58 and cholecystokinin-8 produce similar but not identical activations of myenteric plexus and dorsal vagal complex. Regul Pept 148:88-94
Sullivan, Cherese N; Raboin, Shannon J; Gulley, Stephen et al. (2007) Endogenous cholecystokinin reduces food intake and increases Fos-like immunoreactivity in the dorsal vagal complex but not in the myenteric plexus by CCK1 receptor in the adult rat. Am J Physiol Regul Integr Comp Physiol 292:R1071-80
Goyal, H O; Braden, T D; Williams, C S et al. (2007) Role of estrogen in induction of penile dysmorphogenesis: a review. Reproduction 134:199-208
Goyal, H O; Braden, T D; Cooke, P S et al. (2007) Estrogen receptor alpha mediates estrogen-inducible abnormalities in the developing penis. Reproduction 133:1057-67
Raboin, Shannon J; Gulley, Stephen; Henley, Sheryce C et al. (2006) Atropine methyl nitrate increases myenteric but not dorsal vagal complex Fos-like immunoreactivity in the rat. Physiol Behav 88:448-52
Raboin, Shannon J; Gulley, Stephen; Henley, Sheryce C et al. (2006) Effect of sympathectomy and demedullation on increased myenteric and dorsal vagal complex Fos-like immunoreactivity by cholecystokinin-8. Regul Pept 134:141-8

Showing the most recent 10 out of 29 publications