The Bayliss‐Starling lecture 1973. The gastrointestinal hormones: a review of recent advances.

Gregory, R. A.

doi:10.1113/jphysiol.1974.sp010637

Cited by 97 publications

(34 citation statements)

References 96 publications

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“…The same forms have also been reported in extracts of antral mucosa, or gastrinoma tissue, and have been isolated and sequenced from these sources (16,18,19). It is generally thought that in man the circulating peptides are derived intact from the tissue stores.…”

Section: °Cmentioning

confidence: 78%

Metabolism of heptadecapeptide gastrin in humans studied by region-specific antisera.

Pauwels¹,

Dockray²,

Walker³

et al. 1985

J. Clin. Invest.

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The metabolism of synthetic human heptadecapeptide gastrin (G17) in vivo, and in serum in vitro, was studied by radjoimmunoassay using region specific antisera, gel filtration, ion exchange chromatography, and high performance liquid chromatography. After infusion of G17 intravenously in normal human volunteers, COOH-terminal and NH2-terminal immunoreactive G17 fragments were generated. At a steady state, -15% of COOH-terminal immunoreactivity was attributable to G14-like material and up to 25% of total NH2-terminal immunoreactivity was attributable to two NH2-terminal fragments; one had the chromatographic properties of 1-13 G17, and the other was less acidic and less hydrophobic. After stopping the infusion of G17, the latter fragments accounted for progressively greater proportions of total gastrin activity. When G17 was incubated in serum in vitro, there was timedependent and temperature-dependent loss of immunoreactivity, and again COOH-terminal and NH2-terminal immunoreactive fragments were formed. Removal of the NH2-terminal pyroglutamic acid was probably the rate limiting step because synthetic 2-17 G17 was degraded more rapidly in serum (tl/2, 2-3 h) than G17 (t1/2, 3-5 h). EDTA blocked degradation at the COOH-terminus of both 2-17 G17 and G17 but cleavage at the NH2-terminus still occurred, giving rise to a G14-like peptide. The rate of conversion of G17 in serum was not enough to account for the production of fragments in vivo, and it is proposed that these are formed when G17 encounters enzymes on cell surfaces, perhaps during passage through the capillary circulation. The production of these fragments needs to be considered in interpreting studies of the identity, metabolism, and release of gastrin in health and disease.

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Section: °Cmentioning

confidence: 78%

Metabolism of heptadecapeptide gastrin in humans studied by region-specific antisera.

Pauwels¹,

Dockray²,

Walker³

et al. 1985

J. Clin. Invest.

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“…Pure natural human gastrins, G-17-I and G-34-I, were the generous gifts of Prof. R. A. Gregory and Dr. Hilda Tracy, University of Liverpool. They were purified from a single large gastrin-secreting tumor (3,4) and were free of contaminating peptides. Gastrin solutions were prepared as previously described (5).…”

Section: Methodsmentioning

confidence: 99%

“…Two linear peptides that behave on molecular sieving like these circulating forms have been isolated from gastrin-secreting tumors and their amino acid sequences have been determined (3,4). Human big gastrin (G-34)1 consists of 34 amino acid residues; the single tyrosine residue may be nonsulfated (G-34-I) or sulfated (G-34-II).…”

Section: Introductionmentioning

confidence: 99%

Clearance and acid-stimulating action of human big and little gastrins in duodenal ulcer subjects.

Walsh¹,

Isenberg²,

Ansfield³

et al. 1976

J. Clin. Invest.

123

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A B S T R A C T Acid-stimulating action and clearance of pure natural human big gastrin and little gastrin were assessed in four male subjects with inactive duodenal ulcer (DU) disease. Disappearance half-times for HG-17-I after intravenous infusion (5.2 min) or rapid intravenous injection (6.4 min) were six to eight times shorter than those for HG-34-I (41.5 and 37.8 min, respectively).Studies of clearance of synthetic human little gastrin (HG-17-I) were performed in three of these same four DU subjects, eight additional male DU subjects, and eleven normal male subjects. The disappearance halftime of synthetic HG-17-I averaged 6.2 min in both the DU subjects and the normal subjects. These data suggest that clearance of exogenous gastrin is not altered in patients with DU.Acid secretion in response to rapid intravenous injection of HG-34-I reached a higher peak and lasted longer than in response to an equimolar dose of HG-17-I; the total response to HG-34-I was about three times that to HG-17-I. During constant intravenous infusion, acid responses to equimolar exogenous doses of the two peptides were similar but the increment in molar concentration of circulating gastrin was six to eight times greater with HG-34-I than with HG-17-I.Chromatography of serum obtained during infusions of HG-34-I revealed no evidence of conversion to HG-17-I, nor was there any increase in circulating G-34 activity during infusions of HG-17-I.The increment in serum gastrin concentration required to produce half-maximal stimulation of gastric acid secretion (D50) was estimated in each subject for each gastrin from curves relating acid secretion to change in serum gastrin concentration produced by inThis work was published in part as an abstract: Clin. Res. 23: 259. 1975.

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“…G17 ted to other active C-terminal fragments (Dockray et al, 1981). The C-terminal tetrapeptide of gastrin has all the biological actions of the whole molecule and is shared by cholecystokinin (CCK) (Gregory, 1974). More recently the biologically active C-terminal octapeptide of CCK (CCK8) has been found in high concentrations in brain and peripheral neurones (Rehfeld et al, 1979).…”

Section: Introductionmentioning

confidence: 99%

Renal effects of gastrin C‐terminal tetrapeptide (as pentagastrin) and cholecystokinin octapeptide in conscious rabbit and man

Calam

Gordon

Peart

et al. 1987

British J Pharmacology

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1 Pentagastrin and cholecystokinin octapeptide (CCK8) were infused i.v. at three different doses in two sets of 4 conscious rabbits following a repeated measurements design (130, 1,300 and 13,000 pmol kg-' min-' pentagastrin; 5, 50 and 450 pmol kg-' min-' CCK8). In man, two different doses of pentagastrin (13 and 65 pmol kg-' min-') were infused in two groups of 6 subjects, and CCK8 (2 pmol kg-' min-') in a third group. According to published human postprandial levels, plasma CCK8-like immunoreactivity concentrations were supraphysiological at all doses infused. 2 In the rabbit, pentagastrin produced a dose-related fall in urine flow and free water clearance, but no significant change in systemic and renal haemodynamics, electrolyte excretion and measured plasma constituents; however, in human subjects, pentagastrin increased renal sodium excretion and reduced potassium excretion but did not change glomerular filtration rate. 3 In the rabbit, CCK8 produced a dose-related fall in plasma renin activity, plasma calcium concentration and mean arterial blood pressure; dose-dependent increases in effective renal plasma flow, glomerular filtration rate and renal sodium excretion. In man, changes in sodium and potassium excretion similar to pentagastrin were observed; there were no significant changes in plasma renin activity, plasma calcium concentration, blood pressure, effective renal plasma flow or glomerular filtration rate. 4 The pharmacological renal effects of pentagastrin in conscious water-loaded rabbits resemble vasopressin. In contrast, CCK8's most striking effect was vasodilatation and was unusual in inhibiting rather than stimulating renin release. In man the net changes in urine composition found during infusion of these peptides are similar to those produced by the potassium-sparing diuretics, amiloride and triamterene. However the generally weak renal effects observed, even at pharmacological doses, indicate that these peptides are unlikely to influence renal function under normal physiological conditions.

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The Bayliss‐Starling lecture 1973. The gastrointestinal hormones: a review of recent advances.

Cited by 97 publications

References 96 publications

Metabolism of heptadecapeptide gastrin in humans studied by region-specific antisera.

Metabolism of heptadecapeptide gastrin in humans studied by region-specific antisera.

Clearance and acid-stimulating action of human big and little gastrins in duodenal ulcer subjects.

Renal effects of gastrin C‐terminal tetrapeptide (as pentagastrin) and cholecystokinin octapeptide in conscious rabbit and man

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