Functional and structural characterization of the secretin receptors in rat gastric glands: desensitization and glycoprotein nature.
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.
Bawab
W
W
INSERM U55, Hôpital Saint-Antoine, Paris, France.
Chastre
E
E
Gespach
C
C
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002846:Chromatography, Affinity; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D012633:Secretin / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D008562:Membrane Glycoproteins; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D012633:Secretin; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP