Agents and Actions

, Volume 13, Issue 1, pp 1–4 | Cite as

Diphenhydramine blocks the leukotriene-C4 enhanced mucus secretion in canine tracheain vivo

  • H. G. Johnson
  • R. A. Chinn
  • D. R. Morton
  • M. L. McNee
  • M. D. Miller
  • J. A. Nadel
Histamine and Kinins

Abstract

Leukotrienes (C4, D4) have been shown to enhance mucus seeretion in both isolated human airway tissue and intact canine tracheain vivo. They also have been implicated as putative mediators in several airways diseases. In previous canine studies the mucus enhancing effect of leukotriene-C4 was blocked by atropine, FLP 55,712, and hexamethonium but not by cutting the superior laryngeal and vagus nerves. We anesthetized mongrel dogs with chloralose (100 mg/kg) and urethane (500 mg/kg) and ventilated them on a pump. To visualize the secretions from submucosal glands, we exposed the mucosa of the upper trachea and coated its surface with powdered tantalum. Seeretions from the glands formed elevation in the tantalum layer (hillocks) with time: the number of tracheal hillocks (an index of mucus secretion) was measured at one or more of the four time points on six dogs after each treatment of the treatment sequence: no LTC4, LTC4, no LTC4+ blocker, and LTC4+ blocker. The potential blocker was diphenhydramine, an H1 antagonist for histamine. LTC4 was injected into the cranial thyroid artery which directly feeds the tracheal segment. We observed hillocks through a dissecting microscope, and the number of hillocks per 1.2 cm2 were counted for a 1–4 min interval. In 6 dogs with 12 responses, LTC4 (10 μg) gave a positive response that was significantly different from control (p<0.01–0.05) at 2–4 min.

Diphenhydramine (n=6), 0.5 mg/kg, a dose which blocked a histamine challenge without blocking an acetylcholine challenge of secretion, gave a statistically significant (p<0.01–0.05) reduction in mucus secretion at 1–4 min. These results support the conclusion that leukotriene C4 induces mucus secretion in dogs that is blocked by prior diphenhydramine administration. This would indicate histamine has a role, but as yet an unknown mechanism in the action of leukotriene-C4 in enhancing mucus.

Keywords

Histamine Tantalum Diphenhydramine Mucus Secretion Hexamethonium 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    J.T. Gallagher, P.W. Kent, M. Passatore, R.J. Phipps andP.S. Richardson,The composition of tracheal mucus and the nervous control of its secretion in the cat, Proc. R. Soc. London (Biol.)192, 49–76 (1975).Google Scholar
  2. [2]
    B. Davis, M.G. Marin, S. Fischer, P. Graf, J.G. Widdicombe andJ.A. Nadel,New method for study of canine mucus gland secretion in vivo: cholinergic regulation, Am. Rev. resp. Dis.113, 257, Abst. (1976).PubMedGoogle Scholar
  3. [3]
    J.H. Shelhamer, Z. Marom andM. Kaliner,Immunologic and neuropharmacologic stimulation of mucus glycoprotein release from human airways in vitro, J. clin. Invest.66, 1400–1408 (1980).PubMedGoogle Scholar
  4. [4]
    Z. Marom, J.H. Shelhamer andM. Kaliner,The effects of arachidonic acid, monohydroxyeicosatetraenoic acid, and prostaglandins on the release of mucus glycoproteins from human airways in vitro, J. clin. Invest.69, 1695–1702 (1981).Google Scholar
  5. [5]
    B.A. Jakschik, L.H. Lee, O. Shuffer andC.W. Parker,Aarchidonic acid metabolism is not basophilic leukemia (RBL-1) cells, Prostaglandins16, 733–748 (1978).CrossRefGoogle Scholar
  6. [6]
    L.J. Roberts, R.A. Lewis, J.A. Oates, andK.F. Austen,Prostaglandin, thromboxane and 12-hydroxy 5,8,10,14-eicosatetraenoic acid production by ionophore stimulated art aerosal mast cells, Biochim. biophys. Acta575, 189–192 (1979).Google Scholar
  7. [7]
    M. Hamberg, P. Hedqvist andK. Rodegran,Identification of 15-hydroxy 5,8,11,13-eicosatetraenoic acid (15-HETE) as a major metabolite of arachidonic acid in human lung, Acta physiol. scand.110, 219–221 (1980).PubMedGoogle Scholar
  8. [8]
    R.C. Murphy, S. Hammerström andB. Samuelsson,Leukotriene C: a slow reacting substance from murine mastocytoma cells, Proc. natn Acad. Sci. USA76, 4275–5279 (1979).Google Scholar
  9. [9]
    J.A. Nadel,Autonomic Control of airway smooth muscle and airway secretion, Am. Rev. resp. Dis.115, 117–126 (1977).PubMedGoogle Scholar
  10. [10]
    L. Platshon, andM.A. Kaliner,The effect of the immunologic release of histamine upon human lung cyclic nucleotide levels and prostaglandin generation, J. clin. Invest.62, 1113–1121 (1978).PubMedGoogle Scholar
  11. [11]
    Z. Marom, J.H. Shelhamer, M.K. Bach andM.A. Kaliner,Slow-reacting substances LTC 4 and LTD 4 increase the release of mucus from human airways in vitro. Submitted to Am. Rev. resp. Dis.Google Scholar
  12. [12]
    J.A. Nadel, B. Davis andR.J. Phipps,Control of mucus secretion and ion transport in airways, A. Rev. Physiol.41, 369–381 (1979).CrossRefGoogle Scholar
  13. [13]
    S.E. Dahlen, P. Hedqvist, S. Hammarström andB. Samuelsson.Leukotrienes are potent constrictors of human bronchi, Nature288, 484–486 (1980).CrossRefPubMedGoogle Scholar
  14. [14]
    H.G. Johnson, R.A. Chinn, A.W. Chow, M.K. Bach andJ.A. Nadel,Leukotrienes C 4 enhances the release ofmucus from submucosal glands in canine trachea in vivo, INT. J. Immunopharmacol submitted (1982).Google Scholar
  15. [15]
    H.L. Hahn, A.G. Wilson, P.D. Graf, S.P. Fischer andJ.A. Nadel,Interaction between serotonin and efferent vagus nerves in dog lungs, J. appl. Physiol.44(2), 144–149 (1978).PubMedGoogle Scholar
  16. [16]
    G.K. Adams, andL.L. Lichtenstein,In vitro studies of antigen-induced bronchospasm: Effect of antihistamine and SRS-A antagonist on response of sensitized guinea pig and human airways to antigen, J. Immun.122, 555–562 (1979).PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1983

Authors and Affiliations

  • H. G. Johnson
    • 1
  • R. A. Chinn
    • 2
  • D. R. Morton
    • 1
  • M. L. McNee
    • 1
  • M. D. Miller
    • 1
  • J. A. Nadel
    • 2
  1. 1.Department of Hypersensitivity Diseases ResearchThe Upjohn CompanyKalamazooUSA
  2. 2.Cardiovascular Research Institute and Departments of Physiology and MedicineUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations