A single amino acid of the cholecystokinin-B/gastrin receptor determines specificity for non-peptide antagonists

Abstract

The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases D. Vetrie et al.

Pharmacological evidence for putative CCK1 receptor heterogeneity in human colon smooth muscle

“…It has been established that there are single nucleotide polymorphism (SNP) mutations of human CCK 1 receptors (Tachikawa et al, 2000;Hamann et al, 1999) although their pharmacological properties have not yet been evaluated. SNPs of the related CCK 2 receptor have been shown to aect antagonist binding (Beinborn et al, 1993), therefore, a CCK 1 -receptor SNP-based explanation for the current data seems feasible. Alternatively, the additional binding site identi®ed in the colon may represent an additional isoform of the CCK 1 receptor that is yet to be identi®ed, which may be present either neuronally or within the smooth muscle.…”

Separable Binding Sites for the Natural Agonist Endothelin-1 and the Non-Peptide Antagonist Bosentan on Human Endothelin-A Receptors

“…Single point mutations which differentially affect binding of agonist and antagonist have recently also been described for the cholecystokinin-B/gastrin receptor [37], the NK, receptor for substance P [38, 391 and the adrenergic p2 receptor [40, 411. For endothelin receptors it has been demonstrated, based on studies with chimeric receptor [16-181 that the C-terminal part of the natural agonist endothelin-1 interacts preferably with the region around transmembrane segments 1, 2, 3 and 7. The present study demonstrates a distinct binding site for non-peptide antagonists which differs from this agonist-binding site.…”

Gastrin inhibits cholangiocyte growth in bile duct–ligated rats by interaction with cholecystokinin-B/gastrin receptors viaD -myo-inositol 1,4,5-triphosphate–, Ca2+-, and protein kinase Cα–dependent mechanisms

“…Gastrin receptor belongs to the family of CCK receptors. 16 Two main receptors have been characterized, CCK-A and CCK-B/gastrin, the latter showing a 1,000-fold higher affinity for gastrin. 35,36 Cloning of the CCK-A receptor from pancreas and CCK-B receptor from stomach and brain revealed their heptahelical structure and showed their belonging to the superfamily of guanine nucleotide-binding protein-coupled receptors.…”

“…Gastrin receptor belongs to the family of cholecystokinin (CCK-A and CCK-B) receptors. 16 Gastrin regulates epithelial cell functions through Ca 2ϩ -, D-myo-inositol 1,4,5-triphos-Abbreviations: BDL, bile duct ligation; cAMP, adenosine 3Ј, 5Ј-monophosphate; CCK, cholecystokinin; IP 3 , D-myo-Inositol 1,4,5-triphosphate; PKC, protein kinase C; BSA, bovine serum albumin; ␥-GT, ␥-glutamyl transpeptidase; RIA, radioimmunoassay; L-365,260, (3 R)-3 [NЈ-(3-methylphenyl) ureido]-1,dihydro-1-methyl-5 phenyl-2H1, 4-benzo-diazepin-2-one; L-364,718, 3S-(-)-(1, 3 dihydro-3-(2-indole-carbonyl) amino-1-methyl 5-phenyl-2H-1,4-benzodiazepin-2-one; PBS, phosphate-buffered saline; TBST, Tris-buffered saline; BAPTA/AM, 1,2-bis(2-aminophenoxy)-ethane-N,N,NЈ,NЈ-tetraacetic acid tetrakis(acetxymethyl ester); H7, 1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine; PCNA, proliferating cell nuclear antigen; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; mRNA, messenger RNA. phate (IP 3 )-, and protein kinase C (PKC)-dependent mechanisms.…”