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.
| 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 |
