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gastrin receptors
214
Abstracts from the l lth International Symposium on Regulatory Peptides
STRUCTURAL AND FUNCTIONAL DIVERSITY OF ENDOGENOUS REGULATORY OLIGOPEPTIDES A.A.Zamyatnin AN.Bach Institute of Biochemistry, Russian Academy of Sciences, 33 Leninsky prosp., Moscow 117071 RUSSIA At present we are familiar with more than 1,700 endogenous regulatory oligopeptides involved in the functioning of the nervous, immune, and endocrine systems. More than 130 new primary structures a year are decoded in 37 countries (Fig. 1,2). The information on their structures and functions is contained in a specially created data bank EROP-Moscow (Endogenous Regulatory OligoPeptides) [1]. Most molecules have about 10 amino acid residues although the range chosen was from 2 to 50 (Fig. 3). 150
= .
Fig. 1
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0 lSSO 1~10 1970 1980 1990 Years
0
10
20
30
40
60
Amino acid residue numbe"
Using computer methods [2], a classification of oligopeptides by their primary structure has been performed, which allowed formation of structural and functional families. These families served the basis for studying the common physicochemical and physiological features of regulatory oligopeptides [3]. 1. Zamyatnin A.A. Protein Sequences & Data Analysis, 1991, 4, No 1, 49-52 2. Zamyatnin A.A. Protein Sequences & Data Analysis, 1991, 4, No 1, 53-56 3. Zamyatnin A.A.J. Biochem. Organization, 1992, 1, No 2, 121-138
CHOLECYSTOKININ REGULATES SOMATOSTATIN SECRETION THROUGH BOTH THE CCK-A AND CCK-B/GASTRIN RECEPTORS Yana Zavros and Arthur Shulkes, Department of Surgery, Austin and Repatriation Medical Centre, University of Melbourne, Melbourne, Victoria, Australia. Cholecystokinin (CCK) and gastrin both stimulate gastric somatostatin (SOM) secretion in vitro and thus have the potential to modulate their direct effects on the parietal cell. However, the relative potencies and mechanisms of action of CCK and gastrin on SOM secretion in vivo have not been determined. Nearly all circulating CCK is sulphated compared to only about 50% of circulating gastrin. The objectives of the present study were to compare the in vivo potencies of the sulphated (s) and desulphated (ds) forms of gastrin-17 (G-17) and CCK-8 on SOM secretion, and to determine the nature of the receptors involved by repeating the studies in the presence of the CCK-A (L-364,718) and CCK-B/gastrin (L-365,260) receptor antagonists. Studies were performed in conscious sheep. Results are expressed as the integrated output of plasma SOM, mean + SEM. Statistical analysis was by analysis of variance, P < 0.05. Dose response experiments revealed the following potencies for SOM secretion: G-17s = CCK-8s > G-17ds > > CCK-Sds. Both the CCK-A and CCK-B/gastrin receptor antagonists significantly suppressed CCK-8s-stimulated SOM output (1.03 + 0.25 pmol/l/min to 0.19 + 0.12 pmol/l/min and 0.24 +__ 0.19 pmoi/I/min respectively). In contrast, G17s-stimulated SOM output was inhibited by only the CCK-B/gastrin receptor antagonist. In conclusion, the sulphated forms of CCK and gastrin are more potent than the desulphated forms. Despite sharing a common biologically active carboxy terminus, CCK stimulates SOM secretion by both the CCK-A and CCK-B/gastrin receptors, while gastrin acts via "the CCK-B/gastrin receptor alone. These findings explain in part why CCK is a net inhibitor of gastric acid secretion in vivo.
Abstracts from the l lth International Symposium on Regulatory Peptides
STRUCTURAL AND FUNCTIONAL DIVERSITY OF ENDOGENOUS REGULATORY OLIGOPEPTIDES A.A.Zamyatnin AN.Bach Institute of Biochemistry, Russian Academy of Sciences, 33 Leninsky prosp., Moscow 117071 RUSSIA At present we are familiar with more than 1,700 endogenous regulatory oligopeptides involved in the functioning of the nervous, immune, and endocrine systems. More than 130 new primary structures a year are decoded in 37 countries (Fig. 1,2). The information on their structures and functions is contained in a specially created data bank EROP-Moscow (Endogenous Regulatory OligoPeptides) [1]. Most molecules have about 10 amino acid residues although the range chosen was from 2 to 50 (Fig. 3). 150
= .
Fig. 1
1"m
loo *
m° c= o
~
UKFREber6weCanIta Fra Bel AusN=tD-o°th
o Immmmmmmmm----..~'".~'m Countries
0 lSSO 1~10 1970 1980 1990 Years
0
10
20
30
40
60
Amino acid residue numbe"
Using computer methods [2], a classification of oligopeptides by their primary structure has been performed, which allowed formation of structural and functional families. These families served the basis for studying the common physicochemical and physiological features of regulatory oligopeptides [3]. 1. Zamyatnin A.A. Protein Sequences & Data Analysis, 1991, 4, No 1, 49-52 2. Zamyatnin A.A. Protein Sequences & Data Analysis, 1991, 4, No 1, 53-56 3. Zamyatnin A.A.J. Biochem. Organization, 1992, 1, No 2, 121-138
CHOLECYSTOKININ REGULATES SOMATOSTATIN SECRETION THROUGH BOTH THE CCK-A AND CCK-B/GASTRIN RECEPTORS Yana Zavros and Arthur Shulkes, Department of Surgery, Austin and Repatriation Medical Centre, University of Melbourne, Melbourne, Victoria, Australia. Cholecystokinin (CCK) and gastrin both stimulate gastric somatostatin (SOM) secretion in vitro and thus have the potential to modulate their direct effects on the parietal cell. However, the relative potencies and mechanisms of action of CCK and gastrin on SOM secretion in vivo have not been determined. Nearly all circulating CCK is sulphated compared to only about 50% of circulating gastrin. The objectives of the present study were to compare the in vivo potencies of the sulphated (s) and desulphated (ds) forms of gastrin-17 (G-17) and CCK-8 on SOM secretion, and to determine the nature of the receptors involved by repeating the studies in the presence of the CCK-A (L-364,718) and CCK-B/gastrin (L-365,260) receptor antagonists. Studies were performed in conscious sheep. Results are expressed as the integrated output of plasma SOM, mean + SEM. Statistical analysis was by analysis of variance, P < 0.05. Dose response experiments revealed the following potencies for SOM secretion: G-17s = CCK-8s > G-17ds > > CCK-Sds. Both the CCK-A and CCK-B/gastrin receptor antagonists significantly suppressed CCK-8s-stimulated SOM output (1.03 + 0.25 pmol/l/min to 0.19 + 0.12 pmol/l/min and 0.24 +__ 0.19 pmoi/I/min respectively). In contrast, G17s-stimulated SOM output was inhibited by only the CCK-B/gastrin receptor antagonist. In conclusion, the sulphated forms of CCK and gastrin are more potent than the desulphated forms. Despite sharing a common biologically active carboxy terminus, CCK stimulates SOM secretion by both the CCK-A and CCK-B/gastrin receptors, while gastrin acts via "the CCK-B/gastrin receptor alone. These findings explain in part why CCK is a net inhibitor of gastric acid secretion in vivo.