Gastrin receptors on isolated canine parietal cells
The receptors in the fundic mucosa that mediate gastrin stimulation of acid secretion have been studied. Synthetic human gastrin-17-I (G17) with a leucine substitution in the 15th position ((Leu15)-G17) was iodinated by chloramine T; high saturable binding was found to enzyme-dispersed canine fundic mucosal cells. /sup 127/I-(Leu15)-G17, but not /sup 127/I-G17, retained binding potency and biological activity comparable with uniodinated G17. Fundic mucosal cells were separated by size by using an elutriator rotor, and specific /sup 125/I-(Leu-15)-G17 binding in the larger cell fractions was highly correlated with the distribution of parietal cells. There was, however, specific gastrin binding in the small cell fractions, not accounted for by parietal cells. Using sequential elutriation and stepwise density gradients, highly enriched parietal and chief cell fractions were prepared; /sup 125/I-(Leu15)-G17 binding correlated positively with the parietal cell (r . 0.98) and negatively with chief cell content (r . -0.96). In fractions enriched to 45-65% parietal cells, specific /sup 125/I-(Leu15)-G17 binding was rapid, reaching a steady state at 37 degrees C within 30 min. Dissociation was also rapid, with the rate similar after 100-fold dilution or dilution plus excess pentagastrin. At a tracer concentration from 10 to 30 pM, saturable binding was 7.8 +/- 0.8% per 10(6) cells (mean +/- SE) and binding in the presence of excess pentagastrin accounted for 11% of total binding. G17 and carboxyl terminal octapeptide of cholecystokinin (26-33) were equipotent in displacing tracer binding and in stimulating parietal cell function ((/sup 14/C)aminopyrine accumulation), whereas the tetrapeptide of gastrin (14-17) had a much lower potency. Proglumide inhibited gastrin binding and selectively inhibited gastrin stimulation of parietal cell function.
- Research Organization:
- Center for Ulcer Research and Education, Veterans Administration Wadsworth Hospital Center, Los Angeles, California
- OSTI ID:
- 6729255
- Journal Information:
- J. Clin. Invest.; (United States), Vol. 73:5
- Country of Publication:
- United States
- Language:
- English
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IODINATION
LABELLING
RECEPTORS
CARBON 14 COMPOUNDS
CENTRIFUGATION
GASTRIC ACID
IODINE 127
RADIOCHEMISTRY
STOMACH
TRACER TECHNIQUES
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CHEMICAL REACTIONS
CHEMISTRY
DIGESTIVE SYSTEM
GASTROINTESTINAL TRACT
HALOGENATION
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MATERIALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PEPTIDES
POLYPEPTIDES
PROTEINS
REACTION KINETICS
SEPARATION PROCESSES
STABLE ISOTOPES
550201* - Biochemistry- Tracer Techniques
550901 - Pathology- Tracer Techniques