Action of caerulein and caerulein-like peptides on ?short-circuit current? and acid secretion in the isolated gastric mucosa of amphibians

Negri, Lucia; Erspamer, V.

doi:10.1007/bf00500999

Cited by 20 publications

(3 citation statements)

References 9 publications

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“…C-terminal, non-sulphated fragments of gastrin with thirteen or more amino-acid residues are equipotent with synthetic human gastrin heptadecapeptide, non-sulphate (shG17ns) in both the cat and dog, whilst shorter fragments show a progressive diminution in potency (Hirst, Reed & Shaw, 1977;Strunz, Thompson, Elashoff & Grossman, 1978;Blair, Hirst, Lund, Reed, Sanders & Shaw, 1980;Hirst & Shaw, 1981). Sulphation of the tyrosyl residue in such short fragments is associated with increased potency (Anastasi, Bernardi, Bertaccini, Bosisio, de Castiglione, Erspamer, Goffredo & Impicciatore, 1968;Negri & Erspamer, 1973;de Castiglione, 1977;Hirst, Reed, Shaw, Smeaton, Blair & de Castiglione, 1979). However, the comparison of biological potency based solely upon exogenous doses in vivo does not necessarily reflect the affinity of the peptides for their receptors; differential clearance or delivery rates are likely to contribute significantly to potencies so measured.…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…Gastrin stimulates gastric acid secretion, while CCK causes contraction of the gallbladder and secretion of protein-rich pancreatic juice. The administration of caerulein to mammals produces biological activities similar to those of the above mammalian hormones (2). By the use of sequence-specific antisera, it was shown that gastrinand CCK-like molecules were present in amphibian (3), and it was proposed that caerulein might be an ancestor peptide for mammalian gastrin and CCK.…”

Section: Introductionmentioning

confidence: 99%

Complete nucleotide sequence of mRNA for caerulein precursor fromXenopusskin: the mRNA contains an unusual repetitive structure

1985

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The complete nucleotide sequence of mRNA for caerulein precursor in the skin of Xenopus laevis was determined. The sequence was composed of 705 bp of coding region, accounting for 234 amino acids, 58 bp of 5'-untranslated region and 158 bp of 3'-untranslated region containing two putative poly(A) signals. It coded for four caerulein peptides interspersed with three 147 bp segments (intercaerulein segment; ICS). Analyses of several caerulein encoding cDNAs revealed some interesting features of caerulein mRNA species, which were highly heterogeneous and consisted of a repetition of two fundamental RNA sequences, a 45-nucleotide caerulein fragment and a 147-nucleotide ICS. The result of Northern blotting indicated that caerulein mRNA was only present in frog skin, not in stomach, upper intestine or liver. It appears that caerulein has different physiological function(s) from mammalian gastrin and cholecystokinin-pancreozymin (CCK). The relationship of caerulein to mammalian gastrointestinal hormones is discussed.

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“…There is no evidence that this generalization is justified also in non-mammalian vertebrates. For example, in frog isolated muccsa, caerulein is a more potent stimulant of acid secretion than is gastrin I (Negri & Erspamer 1973) and the relation between peptide structure and effect more closely resembles the relationship of the mammalian gallbladder than the mammalian stomach (discussed by Dockray 1977). Sulphated peptides are more potent than desulphated in eliciting contraction of the Coho salmon gallbladder.…”

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confidence: 99%

Inhibition of gastric acid secretion in the Atlantic cod, Gadus morhua, by sulphated and desulphated gastrin, caerulein, and CCK‐octapeptide

HOLSTEIN

1982

Acta Physiologica Scandinavica

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Gastric acid secretory effects of gastrin/CCK-like peptides have been assayed in cods rendered "spontaneously" secreting by a continuous intestinal perfusion with diluted (33%) seawater. A high dose of pentagastrin induced a weak stimulation (31%) of acid output, while gastrin 17-II, caerulein and CCK8 were inhibitory. Caerulein was the most potent peptide, with an estimated D50 for inhibition of 0.013 nmol/kg.h. Although displaying lower potencies, also the desulphated forms of gastrin-17, caerulein and CCK8 were inhibitory. The results may be explained by release of an endogenous inhibitor, or by interaction with endogenous "codfish gastrin". In the latter case two alternatives are considered: Either gastrin 17, CCK8, and caerulein possess lower efficacies than "codfish gastrin" and therefore act as partial agonists. Alternatively, "codfish gastrin" is itself an inhibitory principle (gastron), the effect of which is mimicked by gastrin 17, caerulein and CCK8. The actions of gastrin and the gastrin-like peptides in the cod indicate a structure-activity relationship different from previously described systems, both mammalian and submammalian.

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Action of caerulein and caerulein-like peptides on ?short-circuit current? and acid secretion in the isolated gastric mucosa of amphibians

Cited by 20 publications

References 9 publications

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

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

Complete nucleotide sequence of mRNA for caerulein precursor fromXenopusskin: the mRNA contains an unusual repetitive structure

Inhibition of gastric acid secretion in the Atlantic cod, Gadus morhua, by sulphated and desulphated gastrin, caerulein, and CCK‐octapeptide

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