Previously, we obtained evidence that specific neuropeptides, such as bombesin-like peptides, thyrotropin-releasing factor, corticotropin-releasing factor, somatostatin, opioid peptides and calcitonin gene-related peptide, act within the brain to influence gastric secretion, contractility and emptying and the ulcerogenic response to stress. These findings and reports by other investigators have delineated a new concept related to brain peptidergic regulation of gastric function. The objectives of the research program will be to develop further such field of investigation to reach a better understanding of brain regulation of gastric secretory and motor function.
The specific aims will be 1) to localize brain sites of action of bombesin, TRH, and CRF to influence gastric function and stress ulceration using microinjection of peptides in specific brain nucleus containing nerve terminal fibers and/or receptors for these peptides 2) to elucidate the neurohumoral pathways mediating the information from brain sites to the stomach using surgical, pharmacological and electrophysiological techniques, 3) to assess the physiologic role of these peptides using selective antagonists and passive immunization. Such studies will yield important information on brain structures, pathways and neurotransmitters involved in brain regulation of gastric function and have relevant implications in the understanding of the pathogenesis of stress ulcer and eating disorders associated with alteration of gastric emptying.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Award (K05)
Project #
5K05MH000663-04
Application #
3075839
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1991-09-01
Budget End
1992-06-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Toth, Karen; Dawson, Geraldine; Meltzoff, Andrew N et al. (2007) Early social, imitation, play, and language abilities of young non-autistic siblings of children with autism. J Autism Dev Disord 37:145-57
Wang, L; Cardin, S; Martinez, V et al. (1999) Duodenal loading with glucose induces fos expression in rat brain: selective blockade by devazepide. Am J Physiol 277:R667-74
Tache, Y; Martinez, V; Million, M et al. (1999) Corticotropin-releasing factor and the brain-gut motor response to stress. Can J Gastroenterol 13 Suppl A:18A-25A
Adelson, D W; Wei, J Y; Yashar, M et al. (1999) Central autonomic activation by intracisternal TRH analogue excites gastric splanchnic afferent neurons. J Neurophysiol 81:682-91
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Martinez, V; Barquist, E; Rivier, J et al. (1998) Central CRF inhibits gastric emptying of a nutrient solid meal in rats: the role of CRF2 receptors. Am J Physiol 274:G965-70
Martinez, V; Wu, S V; Tache, Y (1998) Intracisternal antisense oligodeoxynucleotides to the thyrotropin-releasing hormone receptor blocked vagal-dependent stimulation of gastric emptying induced by acute cold in rats. Endocrinology 139:3730-5
Kaneko, H; Kaunitz, J; Tache, Y (1998) Vagal mechanisms underlying gastric protection induced by chemical activation of raphe pallidus in rats. Am J Physiol 275:G1056-62
Martinez, V; Wang, L; Mayer, E et al. (1998) Proximal colon distention increases Fos expression in the lumbosacral spinal cord and activates sacral parasympathetic NADPHd-positive neurons in rats. J Comp Neurol 390:311-21

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