Structure-activity studies with cholecystokinin on gastric secretion in the cat

Holland, Joy; Hirst, Barry H.; Shaw, B.

doi:10.1016/0196-9781(82)90056-0

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…In agreement with earlier reports on the selectivity of gastrin peptide fragments for gastrin receptors (Morley et al, 1965;Kaminski et al, 1977;Holland et al, 1982;Brand et al, 1984), the shorter C-terminal fragment, TG, appeared to possess low affinity for the CCKA receptor in the gallbladder assay as judged by the lack of effect of 1 liM on the CCK-8 concentration-effect curve. In this study, we apparently achieved selective operational elimination of the gastric muscle CCKB/gastrin receptors using 1 lM TG (Table 1).…”

Section: Discussionsupporting

confidence: 92%

The use of receptor desensitization to analyse CCK_A and CCK_B/gastrin receptors coupled to contraction in guinea‐pig stomach muscle

Bishop

Gerskowitch

Hull

et al. 1995

British J Pharmacology

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Lane, London SE5 9NU 1 The results of previous studies have been in conflict with respect to the involvement of specific cholecystokinin (CCKA) and CCKB/gastrin receptors in guinea-pig gastric muscle. Here . 4 These results indicate that the guinea-pig gastric muscle contains both CCKA-and CCKB/gastrin receptors and the effects of CCK-8 are mediated via both of these receptors. Notwithstanding the complexity of the behaviour of L-365260, it was possible to obtain a reasonable description of the system using a simple 2-receptor model in which the effects of individual receptor activation were assumed to be additive. The absence of a simple competitive interaction of PG with L-365260 may indicate, for example, non-homogeneity of CCKB/gastrin receptors or lack of concentration equilibrium between the bath and the receptor biophase.

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Section: Discussionsupporting

confidence: 92%

The use of receptor desensitization to analyse CCK_A and CCK_B/gastrin receptors coupled to contraction in guinea‐pig stomach muscle

Bishop

Gerskowitch

Hull

et al. 1995

British J Pharmacology

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“…This increase in the number of peptic cells can explain the increase of pepsin content in peptic mucosa. However, no cytological evidence of exocytosis of zymogen granules could be seen after the long-term injections of CCK, although one injection of this peptide is said to be sufficient to increase pepsin secretion (Hersey and Schyberg, 1983;Holland et al, 1982;Kasbekar et al, 1983). Since the mice were killed 8 hr after the last injection of CCK, it was probably too late to observe this phenomenon.…”

Section: Balas Et Almentioning

confidence: 82%

Long‐term comparative effect of cholecystokinin and gastrin on mouse stomach, antrum, intestine, and exocrine pancreas

Balas¹,

Senegas-Balas

Pradayrol

et al. 1985

Am. J. Anat.

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Mice were injected three times a day for 12 days with 300 micrograms/kg body weight of gastrin G17 or 37.5 Ivy dog U/kg body weight of CCK or saline. Other mice were also injected four times an hr for 1 hr with 7.5 micrograms/kg of gastrin, nine Ivy dog U/kg of CCK or saline; 1 hr before killing, they were injected with tritiated thymidine to evaluate the labelling indices in peptic, antral, duodenal, jejunal, and ileal mucosae. Four hours after the first injection of the two peptides, the peptic labelling indices increased while those of intestinal mucosa increased 8 hr after these injections. Long-term injections of CCK had a trophic effect on secretory cells of the digestive tract: the number of gastric zymogenic cells, Paneth cells, and the mucous cells of Brünner glands were hypertrophied. The pepsin, amylase, chymotrypsin, and lysozyme activities increased in stomach, exocrine pancreas, and intestine, respectively. Neither parietal cells nor intestinal enterocytes and hydrolase activities were affected. The trophic effect of long-term injections of gastrin is confirmed on parietal cells and exocrine pancreatic parenchyma and is demonstrated in Paneth cells. Confirming cytological results, pancreatic lipase and amylase activities and intestinal lysozyme activity were increased after gastrin. Although CCK and gastrin have a structural analogy, these two peptides did not affect the same cellular types. A specific action of CCK on the main secretory cells of the digestive mucosa is demonstrated.

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“…We have previously reported pentagastrin (BOC-/?Ala-Trp-Met-Asp-Phe-NH2) to have the same gastric secretary potency as the unblocked gastrin C-terminal pentapeptide (Blair et al 1980). Similarly, addition of a BOC group to the N-terminal of Ser-cholecystokinin hexapeptide is without significant effect on gastric-acid secretary potency (Holland, Hirst & Shaw, 1982b).…”

Section: Influence Of Peptide Lengthmentioning

confidence: 99%

Comparison of effect of peptide length and sulphation on acid secretory potency of gastrin in the cat in vivo and in vitro.

Hirst¹,

Holland²,

Marr³

et al. 1984

The Journal of Physiology

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SUMMARY1. The gastric-acid secretary potency of gastrin peptides was investigated in vivo, in conscious cats prepared with gastric fistula, and in vitro, with kitten isolated gastric mucosae. The influence of peptide length on potency was investigated by comparing synthetic human gastrin heptadecapeptide, non-sulphate (shGl7ns) with a synthetic gastrin butyloxycarbonyl hexapeptide (G6ns), and the influence of sulphation by comparison of G6ns with its sister sulphated peptide (G6s).2. When exogenous doses were compared, shG17ns was the most potent peptide (mean exogenous dose for half-maximal stimulation (EDe0): 0 33 nmol kg-' h1), and was 15-8 times more potent than G6ns (EDe0: 5*14 nmol kg-' h-'). This potency ratio was reduced to 94 when circulating immunoreactive concentrations of the two peptides were compared (mean circulating concentration for half-maximal stimulation (EDc0): shG17ns, 201 pM; G6ns, 1890 pM). The greater potency ratio when exogenous doses were compared was due to the greater metabolic clearance rate (m.c.r.) of the shorter gastrin (m.c.r.: shG17ns, 37 ml kg-' min-; G6ns, 121 ml kg-1 min'). In vitro, shGI7ns (mean concentration for half-maximal stimulation (EC50): 1-99 nM) was 2-8 times more potent than G6ns (EC50: 5.57 nM).3. Sulphation of the hexapeptide increased its potency 3-6-fold when exogenous doses were compared (EDe0 G6s :1-42 nmol kg-1 h'). The greater potency of the sulphated peptide appeared to be due to its lower m.c.r. (20 ml kg-1 min'), and was eliminated when circulating concentrations were compared; potency ratio G6ns: G6s, 1 1.4. We conclude that the increased potency of short gastrin peptides observed upon sulphation is likely to be due to increased resistance to metabolic clearance. Part of the increased potency observed with increasing peptide length can also be explained by increased resistance to clearance, but the small potency difference in vitro may reflect greater affinity for gastrin receptors.

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Structure-activity studies with cholecystokinin on gastric secretion in the cat

Cited by 6 publications

References 14 publications

The use of receptor desensitization to analyse CCK_A and CCK_B/gastrin receptors coupled to contraction in guinea‐pig stomach muscle

The use of receptor desensitization to analyse CCK_A and CCK_B/gastrin receptors coupled to contraction in guinea‐pig stomach muscle

Long‐term comparative effect of cholecystokinin and gastrin on mouse stomach, antrum, intestine, and exocrine pancreas

Comparison of effect of peptide length and sulphation on acid secretory potency of gastrin in the cat in vivo and in vitro.

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Structure-activity studies with cholecystokinin on gastric secretion in the cat

Cited by 6 publications

References 14 publications

The use of receptor desensitization to analyse CCKA and CCKB/gastrin receptors coupled to contraction in guinea‐pig stomach muscle

The use of receptor desensitization to analyse CCKA and CCKB/gastrin receptors coupled to contraction in guinea‐pig stomach muscle

Long‐term comparative effect of cholecystokinin and gastrin on mouse stomach, antrum, intestine, and exocrine pancreas

Comparison of effect of peptide length and sulphation on acid secretory potency of gastrin in the cat in vivo and in vitro.

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The use of receptor desensitization to analyse CCK_A and CCK_B/gastrin receptors coupled to contraction in guinea‐pig stomach muscle

The use of receptor desensitization to analyse CCK_A and CCK_B/gastrin receptors coupled to contraction in guinea‐pig stomach muscle