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


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 


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Copyright information

© Springer-Verlag 1978

Authors and Affiliations

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

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