Structure-function relationships of new synthetic CCK/sub 8/ analogs in rat brain and pancreas

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5385790

Korc, M; Serra, M; Sugg, E; Hruby, V J; Yamamura, H I

Cholecystokinin (CCK) receptors are found in the pancreas, brain, and other tissues. The purpose of the present study was to develop new carboxy-terminal analogs of CCK/sub 8/ to be used as probes for studying CCK receptor heterogeneity. Four analogs of (Nle/sup 28,31)-CCK/sub 26-33/ were therefore prepared. These compounds were evaluated in competition-inhibition studies in rat cortical and pancreatic membranes, using (/sup 3/H)-propionyl-CCK/sub 8/ as the radiolabeled ligand. The N-terminal sulfonamide and N-acetyl derivatives were 3-fold less potent than CCK/sub 8/ in inhibiting pancreatic binding but were equipotent with CCK/sub 8/ in inhibiting cortical binding. The potency of the D-Phe/sup 33/ and L-Leu/sup 33/ N-terminal sulfonamide analogs was greatly reduced in both tissues. All 4 analogs exerted characteristically biphasic effects on amylase release from pancreatic acini, but the potency of D-Phe/sup 33/ and L-Leu/sup 33/ was greatly reduced. The presence of D-Phe or L-Leu in position 33 markedly reduced binding and biological activity of (Nle/sup 28,31/)-CCK/sub 26-33/, whereas the addition of a sulfonamide at its amino-terminal end did not significantly alter either binding or biological activity. These findings suggest that sulfonamide analogs of CCK/sub 8/ may be useful for studying the CCK receptor.

• Research Organization: Univ. of Arizona, Tucson
• OSTI ID: 5385790
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMYLASE
ANIMALS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
DIGESTIVE SYSTEM
ENDOCRINE GLANDS
ENZYMES
GLANDS
GLYCOSYL HYDROLASES
HORMONES
HYDROLASES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
O-GLYCOSYL HYDROLASES
ORGANIC COMPOUNDS
ORGANS
PANCREAS
PEPTIDE HORMONES
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES