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.