The overall goal of this research is to identify specific populations of enteric neurons that are activated by the gut hormones Cholecystokinin (CCK), bombesin and leptin, and to determine the role of CCK receptors, vagus nerve and capsaicin-sensitive neurons in this activation. CCK and nutrients (release CCK (glucose and oleate [fat]), bombesin and leptin (both have synergistic action with CCK) participate in various crucial gastrointestinal functions such as motility or secretion. Also, they play a significant role in the control of food intakeI obesity through evoking many responses such as reduction of food intake and inhibition of gastric emptying. Thus, our first goal is to determine if each of these peptides activate myenteric and sub-mucosal neurons in the rat duodenum, jejunum, ileum, cecum, colon and rectum. The enteric plexuses have numerous neuronal subpopulations, with various shapes and functions. Our second goal is to identify what specific enteric neuronal subpopulations are activated by those stimuli. CCK has two receptors, CCK-A and CCK-B. These receptors mediate different functions in the gastrointestinal tract. Also, there is clear evidence that CCK is either released by nutrients such as fat or glucose when they enter to the small intestine, or act synergistically with bombesin and leptin. Our third goat is to determine the role of each receptor in activation of the enteric neurons by either nutrient, which release CCK or each of the peptides alone or in combination with CCK. The neural control of the gastrointestinal tract is mainly intrinsic. However, the vagus nerve contains the major extrinsic neural supply to the gastrointestinal tract. We suspect that the vagus nerve or the small sensory neurons may have a role in activation of enteric neurons by these peptides and nutrients. Thus, our fourth goal is to determine the role of the vagus nerve and the small sensory neurons in activation ,of the enteric plexuses by the previous peptides or nutrients. We will utilize detection of nuclear Fos as a marker for neuronal activation, and immunoreactivity of five phenotypic markers, NOS, Calbindin, Calretinin, Neurofilament-M and neurokinin-1 receptor.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
2S06GM008091-31
Application #
6547581
Study Section
Minority Programs Review Committee (MPRC)
Project Start
1978-06-01
Project End
2006-06-30
Budget Start
Budget End
Support Year
31
Fiscal Year
2002
Total Cost
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
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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
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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
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

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