This proposal will examine the mechanism by which GI motility is modulated during pregnancy.
Aim 1 will assess the amount of nitric oxide (NO) release following stimulation of the NANC nerves of the GI tract obtained from pregnant rats of different gestational stages using classical pharmacological techniques, and will quantitate the release of NO using a superfusion cascade bioassay.
Aim 2 will assess whether the increased NO release from NANC nerves innervating the GI smooth muscles of the pregnant rat is mediated by estradiol, progesterone, or a combination of both.
Aim 3 will assess whether the increased NO release following NANC nerve stimulation is due to an increase in the amount of neuronal NO synthase (nNOS), and what the cellular and molecular mechanisms involved in this phenomenon are.
Aim 4 will assess whether the decrease in motility of the GI tract and delayed gastric emptying during pregnancy can be reversed by inhibition of NO synthesis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD035991-05
Application #
6499087
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Ilekis, John V
Project Start
1998-02-01
Project End
2005-01-31
Budget Start
2002-02-01
Budget End
2005-01-31
Support Year
5
Fiscal Year
2002
Total Cost
$318,108
Indirect Cost
Name
University of California Los Angeles
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Shah, S; Nathan, L; Singh, R et al. (2001) E2 and not P4 increases NO release from NANC nerves of the gastrointestinal tract: implications in pregnancy. Am J Physiol Regul Integr Comp Physiol 280:R1546-54
Singh, R; Pervin, S; Shryne, J et al. (2000) Castration increases and androgens decrease nitric oxide synthase activity in the brain: physiologic implications. Proc Natl Acad Sci U S A 97:3672-7
Shah, S; Hobbs, A; Singh, R et al. (2000) Gastrointestinal motility during pregnancy: role of nitrergic component of NANC nerves. Am J Physiol Regul Integr Comp Physiol 279:R1478-85