The overall aim is identified as the intention to test whether, in the dorsal vagal complex, neuroactive substances from neuronal and humoral sources ultimately mediate gastric motor excitation or inhibition due to receptor mediated interactions and due to their effects on nitrergic and cholinergic vagal outflow to the stomach. Given this overall conception the investigator proposes two specific aims each with three subpoints. The hypothesis of specific aim 1 is that in the dorsal vagal complex gastric excitatory and inhibitory neuronal inputs independently control basal gastric motility through both nitrergic and cholinergic outflow to the stomach. The second specific aim is to test the hypothesis that selected humoral and therapeutic agents and afferant input act in the DVC to mediate gastric effects dependent on neuronal influences during both basal and reflex stimulated changes in gastric motor function. Sub-aim 2a is do animals rendered unresponsive to nitric oxide TRH and serotonin receptor subtype activation in the dorsal vagal complex respond with expected increases in gastric motor function after endothelin-1 or cisapride. Sub-aim 2b: does cisapride change basal gastric motor function by acting in the DVC and can it act there to alter ET-1 evoked gastric excitation or gastric relaxation in response to colonic distension reflex-evoked gastric changes. Two experiments are proposed for this sub-aim which involve giving cisapride microinjected into the DVC in animals who have been anesthetized and with the dorsal medulla exposed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK042714-10
Application #
6380653
Study Section
Nutrition Study Section (NTN)
Program Officer
May, Michael K
Project Start
1991-08-01
Project End
2003-05-31
Budget Start
2001-06-01
Budget End
2003-05-31
Support Year
10
Fiscal Year
2001
Total Cost
$182,394
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Pharmacology
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112