Vasoactive intestinal peptide and its receptors in fetuses with cystic fibrosis.
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.
Chastre
E
E
Institut National de la Santé et de la Recherche Médicale U.55, Hôpital Saint-Antoine, Paris, France.
Bawab
W
W
Faure
C
C
Emami
S
S
Muller
F
F
Boué
A
A
Gespach
C
C
D000262:Adenylyl Cyclases / Q000378:metabolism; D003550:Cystic Fibrosis / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005333:Fetus; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D007421:Intestine, Small / Q000196:embryology* / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000196:embryology / Q000378:metabolism; D010179:Pancreas / Q000196:embryology / Q000473:pathology; D011247:Pregnancy; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide; D012016:Reference Values; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000494:pharmacology
D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D005934:Glucagon; D000262:Adenylyl Cyclases