Summary
In isolated canine tracheal smooth muscle, repeated administrations of histamine result in a rapid reduction in contractile response to about 15% of the initial contraction (tachyphylaxis). Development of this tachyphylaxis is specific inasmuch as: 1) it does not develop to acetylcholine (10−6 M or 10−4 M), or serotonin (10−5 M); and 2) maximally developed histamine tachyphylaxis is not associated with a parallel reduction in response to acetylcholine. Pretreatment with propranolol (10−5 M) or phentolamine (10−4 M) does not prevent tachyphylaxis: however, pretreatment with atropine (10−4 M) does prevent tachyphylaxis in about 50% of the animals tested.
Tachyphylaxis to histamine can be reversed in a dose- and time-dependent fashion with prostaglandin synthesis inhibiting agents. The order of potency obtained with such compounds (indomethacin > mefenamic acid > oxyphenbutazone > acetylsalicylic acid) is consistent with potencies for inhibition of prostaglandin synthesis found in the literature. Also, in indomethacin pretreated strips in which tachyphylaxis to histamine was prevented, exogenous addition of PGE2 (1.42×10−10 M to 2.84×10−9 M) and PGA2 in a high concentration (2.9×10−9 M) are capable of selectively reducing the response to histamine without an effect on acetylcholine-induced contractions. These data suggest that the mechanism of histamine tachyphylaxis in the canine tracheal smooth muscle preparation involves prostaglandin synthesis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ambrus, J. L., Ambrus, C. M., Harrisson, J. W. E.: Effect of histamine desensitization on histamine induced gastric secretion of guinea pigs. Gastroenterology 18, 249–253 (1951)
Barsoum, G. S., Gaddum, J. H.: The pharmacological estimation of adenosine and histamine in blood. J. Physiol. (Lond.) 85, 1–14 (1935)
Bulbring, E., Burnstock, G.: Membrane potential changes associated with tachyphylaxis and potentiation of the response to stimulating drugs in smooth muscle. Br. J. Pharmacol. 15, 611–624 (1960)
Burn, J. H., Rand, M. J.: The action of sympathomimetic amines in animals treated with reserpine. J. Physiol. (Lond.) 144, 314–336 (1958)
Cantoni, G. L., Eastman, G.: On the response of the intestine to smooth muscle stimulants. J. Pharmacol. Exp. Ther. 87, 392–399 (1946)
Douglas, J. S., Lewis, A. J., Ridgway, P., Brink, C., Bouhuys, A.: Tachyphylaxis to β-adrenoceptor agonists in guinea pig airway smooth muscle in vivo and in vitro. Eur. J. Pharmacol. 42, 195–205 (1977)
Fleisch, J. H., Titus, E.: The prevention of isoproterenol desensitization and isoproterenol reversal. J. Pharmacol. Exp. Ther. 181, 425–433 (1972)
Flower, R. J.: Drugs which inhibit prostaglandin biosynthesis. Pharmacol. Rev. 26, 33–67 (1974)
Flower, R. J., Vane, J. R.: Commentary: Inhibition of prostaglandin biosynthesis. Biochem. Pharmacol. 23, 1439–1450 (1974)
Frey, H. H.: Study into the mechanism of acetylsalicylic acid-induced bronchoconstriction. Pharmacology 15, 529–535 (1977)
Goldstein, A., Aronow, L., Kalman, S. M.: Principles of drug actions: the basis of pharmacology, pp. 569–621. New York: John Wiley & Sons 1974
Gosselin, R. E., Gosselin, R. S.: Tachyphylaxis of guinea pig ileum to histamine and furtrethonium. J. Pharmacol. Exp. Ther. 184, 494–505 (1973)
Grodzinska, L., Panczenko, B., Gryglewski, R. J.: Generation of prostaglandin E-like material by the guinea pig tracheal contracted by histamine. J. Pharm. Pharmacol. 27, 88–91 (1975)
Gryglewski, R. J., Dembinska-Kiec, A., Grodzinska, L., Panczenko, B.: Differential generation of substances with prostaglandin-like and thromboxane-like activities by guinea pig trachea and lung strips. In: Lung cells in disease (A. Bouhuys, ed.), pp. 289–307. New York: North-Holland Publishing Co. 1976
Hawkins, D. F., Schild, H. O.: The action of drugs on isolated human bronchial chains. Br. J. Pharmacol. 6, 682–690 (1951)
Hughes, F. B., McDowall, R. J. S., Soliman, A. A. I.: Sodium choride and smooth muscle. J. Physiol. (Lond.) 134, 256–263 (1956)
Innes, I. R., Nickerson, M.: Atropine, scopolamine and related antimus carinic drugs. In: The pharmacological basis of therapeutics (L. S. Goodman and A. Gilman, eds.) pp. 514–532. New York: MacMillan Publishing Co., Inc. 1975
Kantor, H. S., Hampton, M.: Indomethacin in submicromolar concentrations inhibits cyclic AMP-dependent protein kinase. Nature 276, 841–842 (1978)
Krzanowski, J. J., Anderson, W. H., Polson, J. B., Szentivanyi, A.: Inhibition of the development of histamine tachyphylaxis in canine tracheal smooth muscle by indomethacin. Seventh Int. Congr. Pharmacol., Paris, Abst. no. 2144 (1978)
Lin, C-S., Hurwitz, L., Jenne, J., Avner, B. P.: Mechanism of isoproterenol induced desensitization of tracheal smooth muscle. J. Pharmacol. Exp. Ther. 203, 12–22 (1977)
Loring, S. H., Drazen, J. M., Snapper, J. R., Ingram, R. H.: Vagal and aerosol histamine interactions on airway responses in dogs. J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 45, 40–44 (1978)
Mukherjee, C., Lefkowitz, R. J.: Desensitization of β-adrenergic receptors by β-adrenergic agonists in a cell-free system: Resensitization by guanosine 5′-(B, γ-imino) triphosphate and other purine nucleotides. Proc. Natl. Acad. Sci. 73, 1494–1498 (1976)
Mukherjec, C., Caron, M. G., Lefkowitz, R. J.: Catecholamine-induced subsensitivity of adenylate cyclase associated with loss of β-adrenergic receptor binding sites. Proc. Natl. Acad. Sci. 72, 1945–1949 (1975)
Orehek, J., Douglas, J. S., Bouhuys, A.: Contractile responses of the guinea pig trachea in vitro: Modification by prostaglandin synthesis-inhibitin drugs. J. Pharmacol. Exp. Ther. 194, 555–564 (1975)
Orehek, J., Gayrard, P., Smith, A. P., Grimaud, C., Charpin, J.: Airway responses to carbachol in normal and asthmatic subjects. Am. Rev. Resp. Dis. 115, 937–944 (1977)
Paiva, T. B., Mendes, G. B., Paiva, A. C. M.: Specific desensitization (tachyphylaxis) of the guinea pig ileum to angiotensin. II. Am. J. Physiol. 232, H223-H230 (1977)
Roberts, A. M., Messina, E. J., Kaley, G.: Role of prostaglandins in the mediation of systemic tachyphylaxis to angiotensin. II. Prostaglandins 14, 135–143 (1977)
Stefanovich, V.: Inhibition of 3′,5′-cyclic AMP phosphodiesterase with anti-inflammatory agents. Res. Comm. Chem. Pathol. Pharmacol. 7, 573–582 (1974)
Stephens, N. L.: The mechanics of isolated airway smooth muscle. In: Airway dynamics: physiology and pharmacology (A. Bouhuys, ed.), pp. 191–208. Springfield, Illinois: Charles C. Thomas Co. 1970
Szentivanyi, A., Williams, J. F.: The constitutional basis of atopy. In: Allergic diseases of infancy, childhood, and adolescence (C. W. Bierman and D. S. Pearlman, eds.) (in press), Philadelphia, PA: W. B. Saunders Co. 1979
Van Rossum, J. M.: Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch. Int. Pharmacodyn. 143, 299–330 (1963)
Ward, D.: Pharmacological receptors. Pharmacol. Rev. 20, 49–55 (1968)
Yamaguchi, T., Hitzig, B., Coburn, R. F.: Endogenous prostaglandin and mechanical tension in canine trachealis muscle. Am. J. Physiol. 230, 1737–1743 (1976)
Yen, S. S., Mathe, A. A., Dugan, J. J.: Release of prostaglandins from healthy and sensitized guinea-pig lung and trachea by histamine. Prostaglandins 11, 227–239 (1976)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Anderson, W.H., Krzanowski, J.J., Polson, J.B. et al. Characteristics of histamine tachyphylaxis in canine tracheal smooth muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 308, 117–125 (1979). https://doi.org/10.1007/BF00499053
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00499053