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HISTORY:
In 1964, Gregory and Tracy1 described the isolation of two
heptadecapeptide amides from natural antral mucosa of hogs. They proved to
be remarkably potent stimulators of gastric secretion and offer a wide range of
other activities in the alimentary tract. The two compounds isolated have the
following amino acid sequence:
Pyr-Gly-Pro-Trp-Met-Glu5-Ala-Tyr-Gly-Trp-Met-Asp-Phe-
NH2
which is Gastrin-I. Gastrin-II is the phenolic sulphatemester at the
tyrosine residue in position 12 of Gastrin-I2.
BIOLOGICAL ACTIVITY:
Two of the heptadecapeptide amides we offer differ only from the isolated
products in that the methionine residues are replaced by leucine and
norleucine3. We also offer basic gastrin with the methionine
residue at position 15. The substitution of leucine or norleucine at position 15
does not effect the biological activity as noted by Morley6 wherein
he sites these substitutions. Moreley5 previously showed that the
methionine sulfoxide analog of the C-terminal tetrapeptide amide and almost
certainly of gastrin itself is at most only weakly biologically active. The "15-Met"
HGI we now offer is 99.58% pure by HPLC with Met sulfoxide being its only
contaminant and at less the 1/2 percent. Tracy and Gregory4
described the physiological properties of many peptides structurally related to
Gastrin-I and showed that only the C-terminal tetrapeptide amide:
Trp-Met-Asp-Phe-NH2 was required for biological activity.
SYNTHESIS AND TESTS:
The synthesis of (15-Leucine) Human Gastrin-I was described by Kenner,
et al7 and Wuensch and co-workers8. Biological and
immunological tests of Human Gastrin-I analogues mentioned above are
described by Holle, et al9, Cooke10, Konturek and
Grossman11 and Creutzfeldt, et al12. The biological
activity of partial sequences of the gastrins, especially the action of
Pentagastrin (BOC-b-Ala-Trp-Met-Asp-Phe-NH2 was tested by
Johnson13, Makhlouf, et al14 and
Wormsley15.
REFERENCES:
1. R.A.Gregory and M.J.Tracy, Gut 5, 103 (1964)
2. R.A.Gregory, P.M.Hardy, D.S.Jones, G.W.Kenner,
R.C.Sheppard, Nature 204, 931 (1964)
3. R.A.Gregory, H.J.Tracy and M.J.Grossman, Nature 209, 583
(1966)
4. H.J.Tracy and R.A.Gregory, Nature 204, 935 (1964)
5. J.S.Morley, H.J.Tracy and R.A.Gregory, Nature 207, 1356
(1965)
6.
J.S.Morley, Proc. of the Eighth European Symposium, Nordwijk, Holland,
Sept. 1966, North Holland Publishing co.,Amsterdam, p.226 (1967); J.S.Morley
and J.M.Smith, J.Cjem, Soc., 726 (1968)
7.
G.W.Kenner, J.J.Mendive and R.C.Sheppard, J.Chem.Soc., 726 (1968)
8.
E.Wuensch, B.Konz and F.Holle, Proc. of the International Union of
Physiological Sciences, Munich, 1971, IX S.610
9. B.Konz, F.Holle, E.Wuensch, K.Kissler, F.Leimer,
Z.Gastroent. 9, 413 (1971)
10. A.R.Cooke, Gastroenterolgie, 53, 579 (1967)
11. S.Konturek and M.J.Grossman, Gastroenterology 50, 650
(1966)
12.
G.Tensle, H.Ketterer, H.D.Becker, W.Creutzfeldt, Gatroenterolgie 7, 177
(1972)
13. D.Johnson and K.Jepson, Lancet 17, 585 (1967)
14.
M.G.Makhlout, J.P.A, McManus and W.J.Card, Gastroenterologie 51, 455
(1966)
15. K.G.Wormsley, M.P.Mahoney and G.Kay Gut, 8, 475 (1967)
16. Svensson S.O., Borg I, Emas S, Acid
Responses to histamine pentagastrin human gastrin-I in
conscious cats with gastric fistulas and Heidenhain pouches, Am.J.Digestive Dis.,
16:783-788 (1971)
17. Walsh, J.H., Trout H.H.III, Debas H.T., Grossman, M.I.,
Immunochemical and biological properties of gastrins obtained from
different species and of different molecular species of gastrin., Endocrinology of
the Gut, W.Y.Chey and S.P.Brooks (eds.)
Charles B. Slack, Inc., Thorofare, N.J. 1974 (277-289)
18. Schrumpf E., Semb,L.S., Hunter,W.M., The half life of
synthetic human gastrin in man., Brit.J.Surg., 57:1289-1296 (1973)
19. Cohen,S.,Lipshutz, W. and Hughes, W., Role of gastrin
supersensitivity in the pathogenesis of lower esophageal sphincter
hypertension in achalasia., J.Clin.Invest., 50:1241-1247 (1971)
Typically, all
Gastrin hormones run a minimum of 99% to 100% by HPLC and amino acid
analysis.
Biological activity:
about 1 ug/kg of bodyweight per person equals maximum gastric acid
stimulation.
Maximum rate of infusion not to exceed 2 mcg/kg/hr (950 pmol/kg/hr).
Duration of infusion not to exceed 3 hrs.
Molar ext. coefficient:
12,700 at 280 nm
Storage:
Original dry form Freeze -20oC
Solubility:
Saline or Krebs buffer, also H20
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