Related Experiment Videos
Vasoactive intestinal peptide and its receptors in fetuses with cystic fibrosis
1Institut National de la Santé et de la Recherche Médicale U.55, Hôpital Saint-Antoine, Paris, France.
Insights
Vasoactive intestinal peptide (VIP) levels are elevated in the intestines of fetuses with cystic fibrosis (CF). However, VIP receptors and their function remain unchanged, suggesting VIP is not the cause of CF intestinal defects.
Area of Science:
- Gastroenterology
- Biochemistry
- Pediatric Research
Background:
- Cystic Fibrosis (CF) is a genetic disorder affecting multiple organs, including the intestines.
- Vasoactive Intestinal Peptide (VIP) plays a role in intestinal function and fluid secretion.
- The precise biochemical defect in CF intestines remains incompletely understood.
Purpose of the Study:
- To investigate the role of VIP and its receptors in the pathophysiology of cystic fibrosis in fetal intestines.
- To determine if alterations in VIP levels or receptor function contribute to the intestinal manifestations of CF.
Main Methods:
- Measurement of immunoreactive and biologically active VIP in fetal intestinal tissues (colon and small intestine) and liver (control).
- Analysis of VIP receptor binding characteristics (Scatchard analysis, molecular components) in intestinal mucosa.
- Assessment of VIP receptor-mediated G protein-adenylate cyclase activation.
Main Results:
- VIP content was significantly higher (1.5-2.5 fold) in the colon and lower small intestine of CF fetuses compared to controls.
- No significant differences were observed in VIP receptor binding affinity (Kd), receptor density (Bmax), molecular composition, or functional activation between CF and control groups.
- Similar findings were noted in the liver, a control organ.
Conclusions:
- The study suggests that elevated VIP levels in CF fetal intestines are not due to altered VIP receptors.
- Neither VIP nor its receptors appear to be directly involved in the basic biochemical defect causing intestinal issues in cystic fibrosis.
- Further research is warranted to explore other potential pathways and effectors involved in CF intestinal disease.
Abstract:
Fetuses were investigated to establish whether vasoactive intestinal peptide (VIP) and its receptors are involved in the basic biochemical defect causing cystic fibrosis (CF). The intestine was used as a target for the disease and the liver as control. The immunoreactive and biologically active VIP contents of the colon and lower part of the small intestine were 1.5-2.5 times higher in CF fetuses than in controls. In control and CF intestinal mucosa, there was no change in the Scatchard parameters of the 125I-labeled VIP binding sites (Kd = 4.7-6.1 X 10(-11) M; Bmax = 268-280 fmol/mg protein for the high-affinity sites), in the two molecular components constituting the cross-linked 125I-VIP binding (Mr = 66,000 and 30,000), or in the pharmacological properties and functional characteristics of the VIP receptors activating the G proteins-adenylate cyclase system (Ka = 0.7 X 10(-9) M VIP). Similar results were obtained in liver. These findings suggest that neither VIP nor its receptors are involved in CF intestine. The possible involvement of other effectors related to the VIP pathway in CF intestine, including the release of VIP and adenosine 3',5'-cyclic monophosphate signal-transduction cascade, are presented.