Approximately 25-30% of the US population report gastrointestinal (GI) symptoms compatible with irritable bowel syndrome (IBS). The etiologic mechanisms ascribed to IBS include: 1) altered myoelectric activity, 2) food intolerances and/or inadequate dietary fiber, and 3) hyperawareness of normal bowel function. In the U.S. there is a preponderance of women who report symptoms compatible with IBS suggesting that ovarian hormones may contribute to functional GI changes. This proposal is derived from on-going work on GI symptoms/function in women with and without IBS across the menstrual cycle and the impact of ovarian hormones on GI function in rats (NR01094). Based on preliminary work in a rat model, we are proposing to examine the link between serotonin (5-HT), which is present in both enteric neurons and mucosal enterochromaffin cells, and GI function. Because 5-HT receptors are present on extrinsic fibers innervating the gut and afferent fibers as well as intrinsic neurons, it is hypothesized that 5-HT plays a role in coordinating GI motility and mediating visceral pain. This study will utilize 40 women to be enrolled in the parent project titled """"""""A Nursing Study of Gut Function in Menstruating Women"""""""" (NR-01094). At the time of their laboratory visit (menses, follicular, luteal phase) a blood sample will be obtained from women with IBS (N=20) and without (N=20) IBS or functional bowel distress. Plasma 5-HT will be measured by high performance liquid chromatography (HPLC) and comparisons made with respect to cycle phase and group. A second part of the study will examine intragastric and intraluminal 5-HT content as well as plasma 5-HT in ovariectomized rats receiving estrogen, progesterone, both or placebo. In addition, 5-HT levels will be measured under non-stimulated and stimulated (vagal stimulant; thyrotropin releasing hormone) conditions. 5-HT contents will be measured by HPLC. A 2-way ANOVA procedure will be used to determine the effect of group (ovarian hormone) and stimulation on intragastric and intraluminal 5-HT contents. In a separate group of ovariectomized hormonally treated rats, 5-HT3 receptor radioligand binding studies and autoradiography will be performed to determine the location and binding properties of 5-HT receptors and their modulation by ovarian hormones. This work is perquisite for the use of molecular biology techniques for determination of the regulation of 5-HT receptor gene expression, as well as the role of 5-HT in various physiological/pathological conditions.
