Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 304, Issue 3, pp 237–248 | Cite as

Is histamine involved in the sympathomimetic effect of nicotine?

  • K. Starke
  • R. Weitzell
Article

Summary

Experiments were carried out on superfused strips of the main pulmonary artery of the rabbit in order to examine the proposal that histamine mediates the sympathomimetic effect of nicotine in this tissue. Moreover, effects of serotonin on the nerve endings within the artery were compared with those of nicotine, histamine and tyramine.
  1. 1.

    Pretreatment with with 6-hydroxydopamine intravenously lowered the noradrenaline content of heart and pulmonary artery and enhanced contractions of the latter evoked by noradrenaline. The contractile response to nicotine was abolished even though tissue histamine levels (determined in the heart) and the response to histamine were unchanged.

     
  2. 2.

    (+)-Chlorpheniramine 10−8 M reduced contractions caused by histamine, whereas a concentration of 10−5 M was necessary for a significant antagonism of nicotine effects. This high concentration enhanced the response to exogenous noradrenaline. Although (-)-chlorpheniramine had less than 1/100 the potency of the (+)-enantiomer as an antihistaminic agent, it also reduced the response to nicotine at 10−5 M.

     
  3. 3.

    Phenoxybenzamine irreversibly antagonized the effects of nicotine as well as of histamine and noradrenaline. Receptor protection by a high concentration of histamine failed to preserve the effect of nicotine. On the other hand, protection of α-adrenoceptors by a high concentration of noradrenaline afforded cross-protection against blockade of the effect of nicotine.

     
  4. 4.

    At very high concentrations of histamine, the initial contraction was soon followed by a secondary relaxation. The tissue was then refractory to histamine, but normally sensitive to nicotine and noradrenaline.

     
  5. 5.

    In artery strips preincubated with 3H-noradrenaline, nicotine elicited an immediate increase in the outflow of tritium which peaked in the first 1–2 min and then declined rapidly. In contrast, histamine and serotonin produced slow and progressive increases in tritium outflow.

     
  6. 6.

    Nicotine elicited a transient release of 3H-noradrenaline which was followed by minor increases of 3H-3,4-dihydroxyphenylglycol (DOPEG) and 3H-normetanephrine. Most of the nicotine-evoked outflow of 3H-noradrenaline and 3H-normetanephrine was calcium-dependent. In contrast, the outflow of 3H-DOPEG caused by nicotine 10−3 M was unchanged even when the release of 3H-noradrenaline was almost completely abolished by superfusing with a calciumfree, hexamethonium-containing medium.

     
  7. 7.

    Histamine, serotonin and tyramine elicited a gradual acceleration of 3H-DOPEG outflow which was accompanied by only a very small and (with exceptions mentioned below) progressive and calcium-independent increase in 3H-noradrenaline.

     
  8. 8.

    With serotonin 10−6 and histamine 10−4 peaks of 3H-noradrenaline outflow were obtained in the first 3 min after drug addition. The significance of this finding seems questionable, however, since the peaks were by several orders of magnitude smaller than those caused by nicotine and too small to lead to an increase in the efflux of total tritium. The outflow of 3H-noradrenaline evoked by histamine 10−4 M, but not that evoked by serotonin 10−6 M, was significantly diminished in calcium-free medium.

     
  9. 9.

    In conclusion, no evidence was obtained for a histaminergic link in the sympathomimetic effect of nicotine. All observations are compatible with the view that only noradrenaline mediates the effect, and that the release of noradrenaline is due to a direct action on the nerve endings. The major effects of histamine and serotonin on the noradrenergic nerve terminals could be classified as tyramine-like. No convincing evidence was found for the presence of presynaptic serotonin receptors similar to those previously detected in the rabbit heart and which, like the nicotine receptors, mediate calcium-dependent release of the transmitter.

     

Key words

Rabbit pulmonary artery Presynaptic receptors Nicotine Histamine Serotonin Tyramine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Chiou, C. Y., Trzeciakowski, J., Klein, D. C.: Histamine mediation of nicotine effects on postganglionic sympathetic neuroeffector junctions. Neuropharmacol. 15, 689–693 (1976)Google Scholar
  2. Ehinger, B.: Uptake of histamine or histamine metabolites into sympathetic nonadrenergic axons. Acta physiol. scand. 90, 218–225 (1974)Google Scholar
  3. Endo, T., Starke, K., Bangerter, A., Taube, H. D.: Presynaptic receptor systems on the noradrenergic neurones of the rabbit pulmonary artery. Naunyn-Schmiedeberg's Arch. Pharmacol. 296, 229–247 (1977)Google Scholar
  4. Enero, M. A., Langer, S. Z.: Pharmacological effects of histamine on the isolated cat nictitating membrane. Br. J. Pharmacol. 53, 431P-432P (1975)Google Scholar
  5. Fozard, J. R., Kelly, M. J., Small, R. C.: Chemical sympathectomy of the rabbit with 6-hydroxydopamine. Br. J. Pharmacol. 49, 182P-183P (1973)Google Scholar
  6. Fozard, J. R., Mobarok Ali, A. T. M.: Dual mechanism of the stimulant action of N,N-dimethyl-5-hydroxytryptamine (bufotenine) on cardiac sympathetic nerves. Eur. J. Pharmacol. 49, 25–30 (1978)Google Scholar
  7. Fozard, J. R., Mwaluko, G. M. P.: Mechanism of the indirect sympathomimetic effect of 5-hydroxytryptamine on the isolated heart of the rabbit. Br. J. Pharmacol. 57, 115–125 (1976)Google Scholar
  8. Furchgott, R. F.: Dibenamine blockade in strips of rabbit aorta and its use in differentiating receptors. J. Pharmacol. Exp. Ther. 111, 265–284 (1954)Google Scholar
  9. Furchgott, R. F., Steinsland, O. S., Wakade, T. D.: Studies on prejunctional muscarinic and nicotinic receptors. In: Regulation of catecholamine turnover. Chemical tools in catecholamine research, Vol. II (Almgren, O., Carlsson, A., Engel, J., eds.), pp. 167–174. Amsterdam-Oxford-New York: North-Holland/American Elsevier 1975Google Scholar
  10. Graefe, K. H., Stefano, F. J. E., Langer, S. Z.: Preferential metabolism of (-)-3H-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem. Pharmacol. 22, 1147–1160 (1973)Google Scholar
  11. Langer, S. Z.: Selective metabolic pathways for noradrenaline in the peripheral and in the central nervous system. Med. Biol. 52, 372–383 (1974)Google Scholar
  12. Laverty, R., Taylor, K. M.: The fluorometric assay of catecholamines and related compounds: Improvements and extensions to the hydroxyindole technique. Anal. Biochem. 22, 269–279 (1968)Google Scholar
  13. Leitz, F. H., Stefano, F. J. E.: The effect of tyramine, amphetamine and metaraminol on the metabolic disposition of 3H-norepinephrine released from the adrenergic neuron. J. Pharmacol. Exp. Ther. 178, 464–473 (1971)Google Scholar
  14. Löffelholz, K.: Autoinhibition of nicotinic release of noradrenaline from postganglionic sympathetic nerves. Naunyn-Schmiedeberg's Arch. Pharmacol. 267, 49–63 (1970)Google Scholar
  15. Lorenz, W., Barth, H., Kusche, J., Reimann, H. J., Schmal, A., Matejka, E., Mathias, C., Hutzel, M., Werle, E.: Histamine in the pig: Determination, distribution, release and pharmacological actions. Eur. J. Pharmacol. 14, 155–175 (1971)Google Scholar
  16. Lorenz, W., Matejka, E., Schmal, A., Seidel, W., Reimann, H. J., Uhlig, R., Mann, G.: A phylogenetic study on the occurrence and distribution of histamine in the gastro-intestinal tract and other tissues of man and various animals. Comp. gen. Pharmac. 4, 229–250 (1973)Google Scholar
  17. Luchelli-Fortis, M. A., Langer, S. Z.: Reserpine-induced depletion of the norepinephrine stores: Is it a reliable criterion for the classification of the mechanism of action of sympathomimetic amines? J. Pharmacol. Exp. Ther. 188, 640–653 (1974)Google Scholar
  18. McGrath, M. A.: 5-Hydroxytryptamine and neurotransmitter release in canine blood vessels. Circul. Res. 41, 428–435 (1977)Google Scholar
  19. Muscholl, E.: Cholinomimetic drugs and release of the adrenergic transmitter. In: New aspects of storage and release mechanisms of catecholamines (Schümann, H. J., Kroneberg, G., eds.), pp. 168–186. Berlin-Heidelberg-New York: Springer 1970Google Scholar
  20. Nedergaard, O. A., Schrold, J.: Release of 3H-noradrenaline from incubated and superfused rabbit pulmonary artery. Acta physiol. scand. 89, 296–305 (1973)Google Scholar
  21. Nedergaard, O. A., Schrold, J.: The mechanism of action of nicotine on vascular adrenergic neuroeffector transmission. Eur. J. Pharmacol. 42, 315–329 (1977)Google Scholar
  22. Pluchino, S.: Direct and indirect effects of 5-hydroxytryptamine and tryamine on cat smooth muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 272, 189–224 (1972)Google Scholar
  23. Ross, S. B.: Structural requirements for uptake into catecholamine neurons. In: The mechanism of neuronal and extraneuronal transport of catecholamines (Paton, D. M., ed.), pp. 67–93. New York: Raven Press 1976Google Scholar
  24. Roth, F. E., Govier, W. M.: Comparative pharmacology of chlorpheniramine (chlor-trimeton) and its optical isomers. J. Pharmacol. Exp. Ther. 124, 347–349 (1958)Google Scholar
  25. Rothschild, A. M.: Histamine release by basic compounds. In: Histamine and anti-histaminics, Handbook of experimental pharmacology, Vol. 18/1 (Rocha e Silva, M., ed.), pp. 386–430. Berlin-Heidelberg-New York: Springer 1966Google Scholar
  26. Smith, C. B.: The role of monoamine oxidase in the intraneuronal metabolism of norepinephrine released by indirectly-acting sympathomimetic amines or by adrenergic nerve stimulation. J. Pharmacol. Exp. Ther. 151, 207–220 (1966)Google Scholar
  27. Starke, K.: Regulation of noradrenaline release by presynaptic receptor systems. Rev. Physiol. Biochem. Pharmacol. 77, 1–124 (1977)Google Scholar
  28. Steinsland, O. S., Furchgott, R. F.: Desensitization of the adrenergic neurons of the isolated rabbit earartery to nicotinic agonists. J. Pharmacol. Exp. Ther. 193, 138–148 (1975)Google Scholar
  29. Su, C., Bevan, J. A.: Blockade of the nicotine-induced norepinephrine releaseby cocaine, phenoxybenzamine and desipramine. J. Pharmacol. Exp. Ther. 175, 533–540 (1970)Google Scholar
  30. Taube, H. D., Starke, K., Borowski, E.: Presynaptic receptor systems on the noradrenergic nerones of rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 299, 123–141 (1977)Google Scholar
  31. Trendelenburg, U.: Classification of sympathomimetic amines. In: Catecholamines, Handbook of experimental pharmacology, Vol. 33 (Blaschko, H., Muscholl, E., eds.), pp. 336–362 Berlin-Heidelberg-New York: Springer 1972Google Scholar

Copyright information

© Springer-Verlag 1978

Authors and Affiliations

  • K. Starke
    • 1
  • R. Weitzell
    • 1
  1. 1.Pharmakologisches InstitutUniversität FreiburgFreiburgFederal Republic of Germany

Personalised recommendations