Morbid obesity-associated gastro-oesophageal reflux disease and dyspepsia may be related with a gastrointestinal smooth muscle 5-HT1A receptors-like increased Bmax

Inmaculada Bellido1, Manuel Ruiz2, Jose Luis Gallego2, M Victoria Bellido3, Aurelio Gomez-Luque4. 1Pharmacology and Clinical Therapeutic. Medicine School, Malaga, Spain, 2Surgery S. Carlos Haya Universitary Hospital, Malaga, Spain, 3Intensive Care Unit, Carlos Haya Universitary Hospital, Malaga, Spain, 4S. Anaesthesiology, Virgen Victoria Universitary Hospital, Malaga, Spain.

Background-Aim: Recent studies showed a relationship between obesity and the occurrence of gastrointestinal symptoms, especially of heartburn, regurgitation, hiatus hernia, gastro-oesophageal reflux disease (GERD), dyspepsia (D) and lower abdominal symptoms (1). Increasing body weight has been modestly associated with the onset of dyspeptic symptoms (2) but whether weight gain or loss causes symptoms is unclear. The new orally active 5-HT1A agonist R137696 improved the gastrointestinal dyspepsia by inducing gastrointestinal relaxation in healthy volunteers (3). We hypothesized that morbid obesity’s gastrointestinal disease may be related with a 5-HT1A receptor dysfunction. Thus we compared the gastrointestinal smooth muscle 5-HT1A receptor characteristics from morbid obesity (MO) patients with that obtained from the non-affected biopsy security margin’ smooth muscle from patients subjected to gastrointestinal cancer (GIC) resection.

Methods: We studied the smooth muscle 5-HT1A receptor characteristics by 3H-8OH-DPAT saturation binding experiment in gastrointestinal samples from MO patients treated with bariatric surgery and GIC resection patients. Physiopathological characteristics and clinical stage were recorded. Statistical analyses were stratified by pathology type.

Results: 65 patients with MO (aged 38.9±0.9 years, female 76.9%, BMI 49.5±0.7 kg/m2, laparotomic adjustable gastric banding (53.8%) and laparoscopic Y-Roux gastric bypass (46.2%), a 63.1% with GERD/D were compared with 35 patients with GIC (aged 56.3±1.7 years, female 65.7%, BMI 28.2±0.9 kg/m2, gastric (42.8%) ileum (28,6%) and colon (28,6%) resection with no GERD/no D were compared. The 3H-8OH-DPAT Bmax in MO was 16.5±3.4 fmol/mg of protein and in GIC was 9.2±4.5 fmol/mg of protein (+79.3%, p<0.05, student t test). 3H-8OH-DPAT’s KD in MO was 5.3±0.7 nM and in GIC was 4.6±0.9 nM.

Conclusion: The gastro-oesophageal reflux disease and the dyspepsia associated with morbid obesity may be related with a gastrointestinal smooth muscle 5-HT1A receptor-like increased maximal bound (Bmax).

(1) Van Oijen MGH et al. J Med 64(2):45-9, 2006.
(2) Cremonini F et al. Neurogastroenterol Motil 18:987-94, 2006.
(3) Boeckxstaens GE et al. Neurogastroenterol Motil 18, 919-926,2006.