Details

Autor(en) / Beteiligte

• Hunter, J C
• Suman-Chauhan, N
• Meecham, K G
• Dissanayake, VUK
• Hill, DR
• Pritchard, M C
• Kneen, C O
• Horwell, D C
• Hughes, J
• Woodruff, G N

Titel

( super(3)H)PD 140376: A novel and highly selective antagonist radioligand for the cholecystokinin sub(B)/gastrin receptor in guinea pig cerebral cortex and gastric mucosa

Ist Teil von

• Molecular pharmacology, 1993-01, Vol.43 (4), p.595-602

Erscheinungsjahr

1993

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• The specific binding characteristics of the novel cholecystokinin (CCK) sub(B)/gastrin receptor-selective peptoid antagonist radioligand ( super(3)H)PD 140376 were investigated using membrane homogenates prepared from guinea pig cerebral cortex and gastric fundic mucosa. ( super(3)H)PD 140376 bound to both cerebral cortex and gastric gland homogenates with comparable high affinity and to an apparent single population of sites with B sub(max) values of 119 and 296 fmol/mg of protein, respectively. Pharmacological characterization of the ( super(3)H)PD 140376-labeled binding sites with a series of agonist and antagonist ligands selective for each of the CCK receptor subtypes demonstrated, in both preparations, an affinity profile consistent with that of the CCK sub(B)/gastrin receptor. The affinity and Hill slope for PD 140376 and the related CCK sub(B)/gastrin antagonist CI-988 were unaffected by the presence of the nonhydrolyzable GTP analogue guanylyl-5'-imidodiphosphate. In contrast, guanylyl-5'-imidodiphosphate caused a characteristic decrease in affinity and an increase in the Hill slopes towards unity for the agonist ligands CCK sulfated octapeptide and pentagastrin.