Skip to main content
Log in

Role of Substance P and Calcitonin Gene-Related Peptide in Acid-Induced Augmentation of Opossum Esophageal Blood Flow

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Increased esophageal blood flow may protect against damaging refluxed gastric juices. We have shown that mast cells, histamine, and nitric oxide increase esophageal blood flow in the opossum during acid perfusion. This study examined the roles of substance P and calcitonin gene-related peptide on acid-induced hyperemia and whether the effects of substance P are mediated by mast cells. The opossum distal esophagus was perfused with saline, acid, or capsaicin while blood flow and histamine release were determined. Neuropeptides and neurokinin antagonists were administered parenterally. Only acid or calcitonin gene-related peptide (not substance P or capsaicin) significantly increased blood flow, which was prevented by neurokinin or calcitonin-gene-related peptide antagonists. Acid, substance P, and capsaicin all increased histamine release. Pretreatment with neurokinin antagonists did not affect acid-induced histamine release. We conclude that calcitonin-gene-related peptide is an important mediator of acid-induced esophageal hyperemia, while substance P plays an indirect role.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Morris GP, Feldman MJ, Barclay RL, Paterson WG: Esophagitis as the outcome of progressive failures of the defensive repertoire. Can J Gastroenterol 11(suppl B):28B–36B, 1997

    Google Scholar 

  2. Feldman MJ, Morris GP, Dinda PK, Paterson WG: Mast cells mediate acid-induced augmentation of opossum esophageal blood flow. Gastroenterology 110:121–128, 1996

    Google Scholar 

  3. Trad KS, Fernicola MT, Hakki FZ, Dziki AJ, Harmon JW, Bass BL: Modulation of esophageal blood flow: A local effector function of sensory nerves. Surg Forum 41:122–124, 1990

    Google Scholar 

  4. Sandler AD, Schmidt C, Richardson K, Murray J, Maher JW: Regulation of distal esophageal blood flow: The roles of nitric oxide and substance P. Surgery 114:285–294, 1993

    Google Scholar 

  5. McKie LD, Bass BL, Dunkin BJ, Harmon JW: Nitric oxide regulates basal but not capsaicin-, CGRP-, or bile saltstimulated rabbit esophageal mucosal blood flow. Ann Surg 222:186–192, 1995

    Google Scholar 

  6. McKie LD, Dunkin BJ, Pennannen MF, Dunlap KW, Harmon JW, Bass BL: Esophageal mucosal blood flow: A central role for calcitonin gene-related peptide. Surgery 16:409–418, 1994

    Google Scholar 

  7. Fox P, Fox C, Wolfe S Jr, Cooke HJ: Signalling from the nervous system to the immune system occurs via NK1 receptor occupancy of the mast cell. Gastroenterology 110:A1071, 1996

    Google Scholar 

  8. Geppetti P, Tramontana M, Evangelista S, Renzi D, Maggi CA, Fusco BM, Del Bianco E: Differential effect on neuropeptide release of different concentrations of hydrogen ions on afferent and intrinsic neurons of the rat stomach. Gastroenterology 101:1505–1511, 1991

    Google Scholar 

  9. Ren JY, Wang YP, Liang KX, Gao JS, Brewer K, Harty RF: Mechanisms of proton-induced stimulation of CGRP release from rat antrum. Regul Pept, 59:103–109, 1995

    Google Scholar 

  10. Blennerhasset MG, Tomioka M, Bienenstock J: Formation of contacts between mast cells and sympathetic neurons in vitro. Cell Tissue Res 265:121–128, 1991

    Google Scholar 

  11. Arizono N, Matsuda S, Hattori T, Kojima Y, Maeda T, Galli SJ: Anatomical variation in mast cell nerve associations in the rat small intestine, heart, lung, and skin. Similarities of distances between neural processes and mast cells, eosinophils, or plasma cells in the jejunal lamina propria. Lab Invest 62:626–634, 1990

    Google Scholar 

  12. Cross LJM, Heaney LG, Ennis M: Further characteristics of substance P induced histamine release from human bronchoalveolage lavage mast cells. Inflamm Res 45:S11–S12, 1996

    Google Scholar 

  13. Lilly CM, Hall AE, Rodger IW, Kobzik L, Haley KJ, Drazen JM: Substance P-induced histamine release in tracheally perfused guinea pig lungs. J Appl Physiol 78:1234–1241, 1995

    Google Scholar 

  14. Brunsson I, Fahrenkrug J, Jodal M, Sjöqvist A, Lundgren O: Substance P effects on blood flow, fluid transport, and vasoactive intestinal polypeptide release in the feline small intestine. J Physiol 483:727–734, 1995

    Google Scholar 

  15. Wallace JL, McKnight GW, Befus AD: Capsaicin-induced hyperemia in the stomach: Possible contribution of mast cells. Am J Physiol (Gastrointest Liver Physiol) 263:G209–G214, 1992

    Google Scholar 

  16. Shore PA, Burkhalter A, Cohn VH: A method for the fluorimetric assay of histamine in tissues. J Pharmacol Exp Ther 127:182–186, 1959

    Google Scholar 

  17. Feldman MJ, White RJ, Morris GP, Paterson WG: Low dose pepsin blocks acid-induced hyperemia in the opossum esophagus. Can J Gastroenterol 12(suppl A):115A, 1998

    Google Scholar 

  18. Rival R, Bance M, Antonyshyn O, Phillips J, Pang CY: Comparison of laser Doppler flowmeter and radioactive microspheres in measuring blood flow in pig skin flaps. Laryngoscope 105:383–386, 1995

    Google Scholar 

  19. Zijlstra PK, Hynna-Liepert TT, Dinda PK, Beck IT, Paterson WG: The effect of intraluminal acid on opossum esophageal blood flow. Gastroenterology 98:A155, 1990

    Google Scholar 

  20. Ottosson A, Edvinsson L: Release of histamine from dural mast cells by substance P and calcitonin gene-related peptide. Cephalalgia 17:166–174, 1997

    Google Scholar 

  21. Krumins SA, Broomfield CA: Evidence of NK1 and NK2 tachykinin receptors and their involvement in histamine release in a murine mast cell line. Neuropeptides 21:65–72, 1992

    Google Scholar 

  22. Cocchiara R, Bongiovanni A, Albeggiani G, Azzolina A, Lampiasi N, Di Blasi F, Geraci D: Inhibitory effect of neuraminidase on SP-induced histamine release and TNF-alpha mRNA in rat mast cells: evidence of a receptor-independent mechanism. J Neuroimmunol 75:9–18, 1997

    Google Scholar 

  23. Reymer-Rebuffel AM, Mathiau P, Callebert J, Dimitriadou V, Farjaudon N, Kacem K, Launay JM, Seylaz J, Abineau P: Substance P, calcitonin gene-related peptide, and capsaicin release serotonin from cerebrovascular mast cells. Am J Physiol 267:R1421–1429, 1994

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feldman, M., Morris, G. & Paterson, W. Role of Substance P and Calcitonin Gene-Related Peptide in Acid-Induced Augmentation of Opossum Esophageal Blood Flow. Dig Dis Sci 46, 1194–1199 (2001). https://doi.org/10.1023/A:1010646809166

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1010646809166

Navigation