TRH and 5HT are colocalized in the projections of caudal raphe nuclei onto dorsal vagal complex (DVC) nuclei. TRH and 5HT synergism appears to be involved in the vagal control of gastric function. Microinjections of selective 5HT antagonists will be performed in DVC in order to identify the 5HT receptor subtype involved in the synergistic response. Serotonin release in the dorsal medulla of fed and fasting animals will be compared to document that serotonin release by caudal raphe nuclei projections plays a key role in enhanced acid secretion and motility after a meal. A possible role of excitatory amino acids and substance P as neurotransmitters in the vagal afferents which mediate gastric stimulatory response after a meal will be examined with the use of the agonists and the antagonists of substance P and glutamate. Studies will also be performed to identify DVC neurons (using extracellular recordings) which are activated by gastric distension. Effects and synergistic interactions of TRH and 5HT microinjection directly onto solitary nucleus or DVC nuclei on the """"""""gastric responsive DVC neurons"""""""" will be examined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK047432-02
Application #
2147041
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1994-09-15
Project End
1997-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Ohio State University
Department
Physiology
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Varanasi, Sridhar; Chi, Jinhan; Stephens Jr, Robert L (2002) Methiothepin attenuates gastric secretion and motility effects of vagal stimulants at the dorsal vagal complex. Eur J Pharmacol 436:67-73
Varanasi, S; Chi, J; Rogers, R C et al. (1998) Methiothepin but not methysergide antagonizes TRH effects at the dorsal vagal complex. Ann N Y Acad Sci 861:292-3
Varanasi, S; Chi, J; Stephens Jr, R L (1997) 5-CT or DOI augments TRH analog-induced gastric acid secretion at the dorsal vagal complex. Am J Physiol 273:R1607-11
Chen, C H; Stephens Jr, R L; Rogers, R C (1997) PYY and NPY: control of gastric motility via action on Y1 and Y2 receptors in the DVC. Neurogastroenterol Motil 9:109-16
Chen, C H; Rogers, R C; Stephens Jr, R L (1996) Intracisternal injection of peptide YY inhibits gastric emptying in rats. Regul Pept 61:95-8
Mohammed, J R; Saska, T A; Chi, J et al. (1995) Stimulation of the nucleus raphe obscurus produces marked serotonin release into the dorsal medulla of fed but not fasted rats--glutamatergic dependence. Brain Res 695:100-3