Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Jan;81(2):578–582. doi: 10.1073/pnas.81.2.578

A bombesin immunoreactive peptide in milk.

G D Jahnke, L H Lazarus
PMCID: PMC344722  PMID: 6582513

Abstract

Immunoreactivity to the amphibian peptide bombesin was found in instant nonfat dry milk (ca. 0.7 ng/ml) and in the whey of whole or skim bovine milk (ca. 1.2 ng/ml) even after ultracentrifugation. The soluble immunoreactivity was associated with a peptide exhibiting the following characteristics: (i) parallel displacement in an immunoassay using an antiserum recognizing bombesin amino acid residues 5-8; (ii) separation from both gastrin-releasing peptide and amphibian bombesin by gel filtration--the approximate Mr was 3,200; (iii) denaturation in urea, reduction by dithiothreitol, and acetylation by iodoacetamide had no effect on its elution profile by gel-filtration chromatography and the aggregation of added bombesin to milk proteins or peptides was not observed; (iv) reversed-phase HPLC separated milk immunoreactivity from gastrin-releasing peptide and bombesin; (v) digestion by trypsin yielded a smaller immunoreactive peptide fragment, whereas nearly all immunoreactivity was lost by treatment with alpha-chymotrypsin; and (vi) the level of immunoreactivity was unaffected by boiling. These data show that milk is an exogenous source of bombesin-like immunoreactivity, which may account for the increase of gastric acid and gastrointestinal hormone levels after the consumption of milk.

Full text

PDF
578

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amarant T., Fridkin M., Koch Y. Luteinizing hormone-releasing hormone and thyrotropin-releasing hormone in human and bovine milk. Eur J Biochem. 1982 Oct;127(3):647–650. doi: 10.1111/j.1432-1033.1982.tb06921.x. [DOI] [PubMed] [Google Scholar]
  2. Ayalon A., Yazigi R., Thompson J. C., Devitt P. G., Rayford P. L., Thompson J. C. Direct effect of bombesin on isolated gastric mucosa. Biochem Biophys Res Commun. 1981 Apr 30;99(4):1390–1397. doi: 10.1016/0006-291x(81)90773-7. [DOI] [PubMed] [Google Scholar]
  3. Aynsley-Green A., Lucas A., Bloom S. R. The control of the adaptation of the human neonate to postnatal nutrition. Acta Chir Scand Suppl. 1981;507:269–281. [PubMed] [Google Scholar]
  4. Baram T., Koch Y., Hazum E., Fridkin M. Gonadotropin-releasing hormone in milk. Science. 1977 Oct 21;198(4314):300–302. doi: 10.1126/science.333582. [DOI] [PubMed] [Google Scholar]
  5. Basso N., Lezoche E., Giri S., Percoco M., Speranza V. Acid and gastrin levels after bombesin and calcium infusion in patients with incomplete antrectomy. Am J Dig Dis. 1977 Feb;22(2):125–128. doi: 10.1007/BF01072954. [DOI] [PubMed] [Google Scholar]
  6. Bertaccini G., Erspamer V., Melchiorri P., Sopranzi N. Gastrin release by bombesin in the dog. Br J Pharmacol. 1974 Oct;52(2):219–225. doi: 10.1111/j.1476-5381.1974.tb09703.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blanc B. Biochemical aspects of human milk--comparison with bovine milk. World Rev Nutr Diet. 1981;36:1–89. doi: 10.1159/000393152. [DOI] [PubMed] [Google Scholar]
  8. Boat T. F., Cheng P. W., Iyer R. N., Carlson D. M., Polony I. Human respiratory tract secretion. Mucous glycoproteins of nonpurulent tracheobronchial secretions, and sputum of patients with bronchitis and cystic fibrosis. Arch Biochem Biophys. 1976 Nov;177(1):95–104. doi: 10.1016/0003-9861(76)90419-7. [DOI] [PubMed] [Google Scholar]
  9. Brown M. R., Rivier J., Vale W. W. Bombesin affects the central nervous system to produce hyperglycemia in rats. Life Sci. 1977 Dec 15;21(12):1729–1734. doi: 10.1016/0024-3205(77)90151-5. [DOI] [PubMed] [Google Scholar]
  10. Brown M., Allen R., Villarreal J., Rivier J., Vale W. Bombesin-like activity: radioimmunologic assessment in biological tissues. Life Sci. 1978 Dec 31;23(27-28):2721–2728. doi: 10.1016/0024-3205(78)90652-5. [DOI] [PubMed] [Google Scholar]
  11. Brown M., Märki W., Rivier J. Is gastrin releasing peptide mammalian bombesin? Life Sci. 1980 Jul 14;27(2):125–128. doi: 10.1016/0024-3205(80)90453-1. [DOI] [PubMed] [Google Scholar]
  12. Brown M., Rivier J., Vale W. Bombesin:potent effects on thermoregulation in the rat. Science. 1977 May 27;196(4293):998–1000. doi: 10.1126/science.860130. [DOI] [PubMed] [Google Scholar]
  13. Carpenter G. Epidermal growth factor is a major growth-promoting agent in human milk. Science. 1980 Oct 10;210(4466):198–199. doi: 10.1126/science.6968093. [DOI] [PubMed] [Google Scholar]
  14. Corazziari E., Delle Fave G., Pozzessere C., Kohn A., de Magistris L., Anzini F., Torsoli A. Effect of bombesin on lower esophageal sphincter pressure in humans. Gastroenterology. 1982 Jul;83(1 Pt 1):10–14. [PubMed] [Google Scholar]
  15. Delle Fave G., Kohn A., de Magistris L., Mancuso M., Sparvoli C. Effect of bombesin-stimulated gastrin on gastric acid secretion in man. Life Sci. 1980 Sep 15;27(11):993–999. doi: 10.1016/0024-3205(80)90110-1. [DOI] [PubMed] [Google Scholar]
  16. DuVal J. W., Saffouri B., Weir G. C., Walsh J. H., Arimura A., Makhlouf G. M. Stimulation of gastrin and somatostatin secretion from the isolated rat stomach by bombesin. Am J Physiol. 1981 Sep;241(3):G242–G247. doi: 10.1152/ajpgi.1981.241.3.G242. [DOI] [PubMed] [Google Scholar]
  17. Engler D., Scanlon M. F., Jackson I. M. Thyrotropin-releasing hormone in the systemic circulation of the neonatal rat is derived from the pancreas and other extraneural tissues. J Clin Invest. 1981 Mar;67(3):800–808. doi: 10.1172/JCI110097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Erb R. E., Sitarz E., Malven P. V. Blood plasma and milk prolactin, and effects of sampling technique on composition of milk from suckled ewes. J Dairy Sci. 1977 Feb;60(2):197–203. doi: 10.3168/jds.s0022-0302(77)83854-x. [DOI] [PubMed] [Google Scholar]
  19. Erisman M. D., Linnoila R. I., Hernandez O., DiAugustine R. P., Lazarus L. H. Human lung small-cell carcinoma contains bombesin. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2379–2383. doi: 10.1073/pnas.79.7.2379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gala R. R., Forsyth I. A., Turvey A. Milk prolactin is biologically active. Life Sci. 1980 Mar 24;26(12):987–993. doi: 10.1016/0024-3205(80)90121-6. [DOI] [PubMed] [Google Scholar]
  21. Gala R. R., Singhakowinta A., Brennan M. J. Studies on prolactin in human serum, urine and milk. Horm Res. 1975;6(5-6):310–320. doi: 10.1159/000178680. [DOI] [PubMed] [Google Scholar]
  22. Ghatei M. A., Jung R. T., Stevenson J. C., Hillyard C. J., Adrian T. E., Lee Y. C., Christofides N. D., Sarson D. L., Mashiter K., MacIntyre I. Bombesin: action on gut hormones and calcium in man. J Clin Endocrinol Metab. 1982 May;54(5):980–985. doi: 10.1210/jcem-54-5-980. [DOI] [PubMed] [Google Scholar]
  23. Grosvenor C. E., Whitworth N. S. Incorporation of rat prolactin into rat milk in vivo and in vitro. J Endocrinol. 1976 Jul;70(1):1–9. [PubMed] [Google Scholar]
  24. Hazum E., Sabatka J. J., Chang K. J., Brent D. A., Findlay J. W., Cuatrecasas P. Morphine in cow and human milk: could dietary morphine constitute a ligand for specific morphine (mu) receptors? Science. 1981 Aug 28;213(4511):1010–1012. doi: 10.1126/science.6267691. [DOI] [PubMed] [Google Scholar]
  25. Hirschowitz B. I., Gibson R. G. Stimulation of gastrin release and gastric secretion: effect of bombesin and a nonapeptide in fistula dogs with and without fundic vagotomy. Digestion. 1978;18(3-4):227–239. doi: 10.1159/000198206. [DOI] [PubMed] [Google Scholar]
  26. Jahnke G. D., Lazarus L. H., DiAugustine R. P., Soldato C. M., Erisman M. D. Peptide hormone degradation by a rat mast cell chymase-heparin complex. Life Sci. 1981 Jul 27;29(4):397–403. doi: 10.1016/0024-3205(81)90333-7. [DOI] [PubMed] [Google Scholar]
  27. Koldovsky O. Hormones in milk. Life Sci. 1980 Jun 2;26(22):1833–1836. doi: 10.1016/0024-3205(80)90610-4. [DOI] [PubMed] [Google Scholar]
  28. Lazarus L. H., DiAugustine R. P., Jahnke G. D., Hernandez O. Physalaemin: an amphibian tachykinin in human lung small-cell carcinoma. Science. 1983 Jan 7;219(4580):79–81. doi: 10.1126/science.6294828. [DOI] [PubMed] [Google Scholar]
  29. Lazarus L. H., Perrin M. H., Brown M. R. Mast cell binding of neurotensin. I. Iodination of neurotensin and characterization of the interaction of neurotensin with mast cell receptor sites. J Biol Chem. 1977 Oct 25;252(20):7174–7179. [PubMed] [Google Scholar]
  30. LeRoith D., Shiloach J., Roth J., Lesniak M. A. Insulin or a closely related molecule is native to Escherichia coli. J Biol Chem. 1981 Jul 10;256(13):6533–6536. [PubMed] [Google Scholar]
  31. Malven P. V. Prolactin and other protein hormones in milk. J Anim Sci. 1977 Sep;45(3):609–616. doi: 10.2527/jas1977.453609x. [DOI] [PubMed] [Google Scholar]
  32. Mazzanti G., Falconieri Erspamer G., Piccinelli D. Relative potencies of porcine bombesin-like heptacosapeptide (PB-27), amphibian bombesin (B-14) and litorin, and bombesin C-terminal nonapeptide (B-9) on in vitro and in vivo smooth muscle preparations. J Pharm Pharmacol. 1982 Feb;34(2):120–121. doi: 10.1111/j.2042-7158.1982.tb04200.x. [DOI] [PubMed] [Google Scholar]
  33. McClelland D. B. Antibodies in milk. J Reprod Fertil. 1982 Jul;65(2):537–543. doi: 10.1530/jrf.0.0650537. [DOI] [PubMed] [Google Scholar]
  34. McDonald T. J., Ghatei M. A., Bloom S. R., Adrian T. E., Mochizuki T., Yanaihara C., Yanaihara N. Dose-response comparisons of canine plasma gastroenteropancreatic hormone responses to bombesin and the porcine gastrin-releasing peptide (GRP). Regul Pept. 1983 Jan;5(2):125–137. doi: 10.1016/0167-0115(83)90120-9. [DOI] [PubMed] [Google Scholar]
  35. McDonald T. J., Ghatei M. A., Bloom S. R., Track N. S., Radziuk J., Dupre J., Mutt V. A qualitative comparison of canine plasma gastroenteropancreatic hormone response to bombesin and the porcine gastrin-releasing peptide (GRP). Regul Pept. 1981 Sep;2(5):293–304. doi: 10.1016/0167-0115(81)90034-3. [DOI] [PubMed] [Google Scholar]
  36. McDonald T. J., Jörnvall H., Ghatei M., Bloom S. R., Mutt V. Characterization of an avian gastric (proventricular) peptide having sequence homology with the porcine gastrin-releasing peptide and the amphibian peptides bombesin and alytesin. FEBS Lett. 1980 Dec 15;122(1):45–48. doi: 10.1016/0014-5793(80)80398-x. [DOI] [PubMed] [Google Scholar]
  37. McDonald T. J., Jörnvall H., Nilsson G., Vagne M., Ghatei M., Bloom S. R., Mutt V. Characterization of a gastrin releasing peptide from porcine non-antral gastric tissue. Biochem Biophys Res Commun. 1979 Sep 12;90(1):227–233. doi: 10.1016/0006-291x(79)91614-0. [DOI] [PubMed] [Google Scholar]
  38. Meuris S., Verloes A., Robyn C. Immunocytochemical localization of prolactin-like immunoreactivity in rat pancreatic islets. Endocrinology. 1983 Jun;112(6):2221–2223. doi: 10.1210/endo-112-6-2221. [DOI] [PubMed] [Google Scholar]
  39. Minamino N., Kangawa K., Matsuo H. Neuromedin B: a novel bombesin-like peptide identified in porcine spinal cord. Biochem Biophys Res Commun. 1983 Jul 29;114(2):541–548. doi: 10.1016/0006-291x(83)90814-8. [DOI] [PubMed] [Google Scholar]
  40. Moldoveanu Z., Tenovuo J., Mestecky J., Pruitt K. M. Human milk peroxidase is derived from milk leukocytes. Biochim Biophys Acta. 1982 Sep 17;718(1):103–108. doi: 10.1016/0304-4165(82)90014-9. [DOI] [PubMed] [Google Scholar]
  41. Moody T. W., Pert C. B. Bombesin-like peptides in rat brain: quantitation and biochemical characterization. Biochem Biophys Res Commun. 1979 Sep 12;90(1):7–14. doi: 10.1016/0006-291x(79)91582-1. [DOI] [PubMed] [Google Scholar]
  43. Petrusz P., Merchenthaler I., Maderdrut J. L., Vigh S., Schally A. V. Corticotropin-releasing factor (CRF)-like immunoreactivity in the vertebrate endocrine pancreas. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1721–1725. doi: 10.1073/pnas.80.6.1721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Pontiroli A. E., Alberetto M., Restelli L., Facchinetti A. Effect of bombesin and ceruletide on prolactin, growth hormone, luteinizing hormone, and parathyroid hormone release in normal human males. J Clin Endocrinol Metab. 1980 Dec;51(6):1303–1305. doi: 10.1210/jcem-51-6-1303. [DOI] [PubMed] [Google Scholar]
  45. Reeve J. R., Jr, Walsh J. H., Chew P., Clark B., Hawke D., Shively J. E. Amino acid sequences of three bombesin-like peptides from canine intestine extracts. J Biol Chem. 1983 May 10;258(9):5582–5588. [PubMed] [Google Scholar]
  46. Reppert S. M., Klein D. C. Transport of maternal[3H]melatonin to suckling rats and the fate of [3H]melatonin in the neonatal rat. Endocrinology. 1978 Feb;102(2):582–588. doi: 10.1210/endo-102-2-582. [DOI] [PubMed] [Google Scholar]
  47. Roth K. A., Evans C. J., Lorenz R. G., Weber E., Barchas J. D., Chang J. K. Identification of gastrin releasing peptide-related substances in guinea pig and rat brain. Biochem Biophys Res Commun. 1983 Apr 29;112(2):528–536. doi: 10.1016/0006-291x(83)91497-3. [DOI] [PubMed] [Google Scholar]
  48. Rökaeus A., McDonald T. Release of neurotensin-like immunoreactivity (NTLI) from rat intestine following administration of bombesin. Acta Physiol Scand. 1980 Nov;110(3):326–326. doi: 10.1111/j.1748-1716.1980.tb06672.x. [DOI] [PubMed] [Google Scholar]
  49. Sarda A. K., Nair R. M. Elevated levels of LRH in human milk. J Clin Endocrinol Metab. 1981 Apr;52(4):826–828. doi: 10.1210/jcem-52-4-826. [DOI] [PubMed] [Google Scholar]
  50. Schusdziarra V., Rouiller D., Harris V., Pfeiffer E. F., Unger R. H. Effect of bombesin upon plasma somatostatin-like immunoreactivity, insulin and glucagon in normal and chemically sympathectomized dogs. Regul Pept. 1980 Oct;1(2):89–96. doi: 10.1016/0167-0115(80)90013-0. [DOI] [PubMed] [Google Scholar]
  51. Strbák V., Alexandrová M., Macho L., Ponec J. Transport of 3H-TRH from plasma to rat milk: accumulation and slow degradation in milk and presence of unaltered hormone in gastric content of pups. Biol Neonate. 1980;37(5-6):313–321. doi: 10.1159/000241293. [DOI] [PubMed] [Google Scholar]
  52. Tenore A., Oberkotter L. V., Koldovskỳ O., Parks J. S., Vandenberg C. M. Thyrotropin in human breast milk. Horm Res. 1981;14(4):193–200. doi: 10.1159/000179388. [DOI] [PubMed] [Google Scholar]
  53. Track N. S., Cutz E. Bombesin-like immunoreactivity in developing human lung. Life Sci. 1982 May 3;30(18):1553–1556. doi: 10.1016/0024-3205(82)90243-0. [DOI] [PubMed] [Google Scholar]
  54. Varner A. A., Modlin I. M., Walsh J. H. High potency of bombesin for stimulation of human gastrin release and gastric acid secretion. Regul Pept. 1981 Jan;1(4):289–296. doi: 10.1016/0167-0115(81)90052-5. [DOI] [PubMed] [Google Scholar]
  55. Villarreal J. A., Brown M. R. Bombesin-like peptide in hypothalamus: chemical and immunological characterization. Life Sci. 1978 Dec 31;23(27-28):2729–2733. doi: 10.1016/0024-3205(78)90653-7. [DOI] [PubMed] [Google Scholar]
  56. Whitworth N. S., Grosvenor C. E. Transfer of milk prolactin to the plasma of neonatal rats by intestinal absorption. J Endocrinol. 1978 Nov;79(2):191–199. doi: 10.1677/joe.0.0790191. [DOI] [PubMed] [Google Scholar]
  57. Yanaihara N., Yanaihara C., Mochizuki T., Iwahara K., Fujita T., Iwanaga T. Immunoreactive GRP. Peptides. 1981;2 (Suppl 2):185–191. doi: 10.1016/0196-9781(81)90029-2. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES