A Novel Reporter Gene Assay to Determine Estrogen Receptor Activity in Primary Breast Cancer Cells

Abstract

diarrhoea-predominant IBS with increased 5HT release but whether reduced release plays a role in causing constipation has not been examined. Aims: To determine the relationship between postprandial plasma serotonin release and colonic transit in C-IBS compared with PI-IBS and healthy controls. Methods: 15 C-IBS, 15 PI-IBS with diarrhoea predominant symptoms, and 15 healthy volunteers recruited through advertisement, underwent serial plasma serotonin measurement after a standard 520 kcal meal for 3 hours. Blood was taken through an 18G cannula into a syringe containing citrate, adenosine, dipyrimadole and theophylline to inhibit platelet activation. Platelet poor plasma (PPP) and platelet rich plasma (PRP) was assessed for 5-HT using H P K with electrochemical detection. Colonic transit was measured using marker pellets. Results: Mean (SEM) colonic transit was prolonged in C-IBS (49.4i3.8hrs) compared to PI-IBS (26.7e4.5) and controls (34.1d.5) ( ~ 4 . 0 0 2 ) . The area under the curve (AUC) of PPP serotonin from immediately after the meal to 180 minutes was lower in C-IBS (2593009nmoVL.min) compared to PI-IBS (5623i721) and controls (4822698) (p<O.OOI). Although PI-IBS showed increased AUC compared to controls these differences were not significant owing to substantial variability. There was a negative correlation between AUC and transit in all subjects ( ~ 0 . 3 5 4 , p=0.02). Platelet 5HT was greater in C-IBS (652k56.1) compared to PI-IBS (PRP= 484.1dO.7 ng/109 platelets), ~ 4 . 0 3 9 ) but not significantly different from controls (598.5i36.4) Conclusions: Reduced 5-HT release may be an important contributor to slow intestinal transit in C-IBS.