1. Functional and structural characterization of the secretin receptors in rat gastric glands: desensitization and glycoprotein nature.
- Author
-
Bawab W, Chastre E, and Gespach C
- Subjects
- Animals, Binding Sites drug effects, Chromatography, Affinity, Colforsin pharmacology, Cyclic AMP metabolism, Down-Regulation drug effects, Gastric Mucosa drug effects, Glucagon-Like Peptide 1, Male, Membrane Glycoproteins drug effects, Peptides pharmacology, Radioligand Assay, Rats, Rats, Inbred Strains, Receptors, G-Protein-Coupled, Receptors, Gastrointestinal Hormone antagonists & inhibitors, Receptors, Gastrointestinal Hormone drug effects, Secretin antagonists & inhibitors, Secretin pharmacology, Time Factors, Vasoactive Intestinal Peptide pharmacology, Gastric Mucosa metabolism, Membrane Glycoproteins metabolism, Receptors, Gastrointestinal Hormone metabolism, Secretin metabolism
- Abstract
We have documented and characterized the down-regulation of the 125I-secretin binding sites and the associated desensitization of the secretin receptor-cAMP system in rat gastric glands. Secretin induced a rapid decrease of the high-affinity 125I-secretin binding sites with t1/2 = 30 min at 37 degrees C. Half-maximal down-regulation and desensitization occurred at 10(-9) M secretin, a physiological concentration corresponding to the half-maximal activation of the secretin receptor. The Scatchard parameters of the low-affinity 125I-secretin binding sites were unaffected by the pretreatment. This desensitization is heterologous in view of the loss of responsiveness to the truncated glucagon-like peptide 1 (TGLP-1), and pharmacologically selective since the secretin-related analogue VIP (10(-7) M) does not alter the secretin-induced cAMP generation in rat gastric glands. The glycoprotein nature of the secretin receptor has also been demonstrated using WGA-agarose affinity chromatography of the solubilized 125I-secretin receptor complex. more...
- Published
- 1991
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