Skip to main content
SpringerLink
Log in

Pre- and postsynaptic effects of yohimbine stereoisomers on noradrenergic transmission in the pulmonary artery of the rabbit

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Effects on noradrenergic neurotransmission of five stereoisomers of yohimbine and of the closely related compound yohimbol were studied in strips of the pulmonary artery of the rabbit. In some experiments the tissue was preincubated with 3H-noradrenaline. Three effects were observed. Firstly, antagonism to the contractile effect of noradrenaline and of sympathetic nerve stimulation; the antagonism reflected competitive blockade of postsynaptic α-adrenoceptors. Secondly, an increase in the stimulation-evoked overflow of total tritium and 3H-noradrenaline; the increase appeared to be due to blockade of presynaptic α-adrenoceptors. Thirdly, an increase in the basal outflow of 3H-3,4-dihydrophenylglycol, presumably by impairment of the vesicular storage of 3H-noradrenaline. According to their relative potencies in eliciting these effects, the drugs could be divided into three groups. Rauwolscine, β-yohimbine and yohimbol preferentially blocked the presynaptic α-adrenoceptor; rauwolscine and β-yohimbine, like yohimbine, at low concentrations increased the contractile response to sympathetic nerve stimulation. Corynanthine preferentially blocked the postsynaptic α-adrenoceptor. Pseudoyohimbine and 3-epi-α-yohimbine were very weak antagonists at either receptor; they mainly accelerated the basal outflow of 3H-3,4-dihydroxyphenylglycol.

From these results and those of a previous study it is concluded that, in a series of twelve α-adrenolytic drugs, rauwolscine shows the greatest preference for presynaptic and corynanthine the greatest preference for postsynaptic α-adrenoceptors. In view of the chemical similarity of the two compounds these opposite properties are striking. Corynanthine and rauwolscine might be useful tools for the subclassification of α-adrenoceptors.

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

Access this article

Log in via an institution

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

  • Adler-Graschinsky, E., Langer, S. Z., Rubio, M. C.: Metabolism of norepinephrine released by phenoxybenzamine in isolated guinea-pig atria. J. Pharmacol. Exp. Ther. 180, 286–301 (1972)

    Google Scholar 

  • Arunlakshana, O., Schild, H. O.: Some quantitative uses of drug antagonists. Br. J. Pharmacol. 14, 48–58 (1959)

    Google Scholar 

  • Berthelsen, S., Pettinger, W. A.: A functional basis for classification of α-adrenergic receptors. Life Sci. 21, 595–606 (1977)

    Google Scholar 

  • Bevan, J. A.: Norepinephrine and the presynaptic control of adrenergic transmitter release. Fed. Proc. 37, 187–190 (1978)

    Google Scholar 

  • Blakeley, A. G. H., Summers, R. J.: The effects of piperoxan on uptake of noradrenaline and overflow of transmitter in the isolated blood perfused spleen of the cat. Br. J. Pharmacol. 63, 683–687 (1978)

    Google Scholar 

  • Borowski, E., Starke, K., Ehrl, H., Endo, T.: A comparison of pre- and postsynaptic effects of α-adrenolytic drugs in the pulmonary artery of the rabbit. Neuroscience 2, 285–296 (1977)

    Google Scholar 

  • Brown, D. A., Caulfield, M. P.: Hyperpolarizing ‘α2’-adrenoceptors in rat sympathetic ganglia. Br. J. Pharmacol. 65, 435–445 (1979)

    Google Scholar 

  • Butler, M., Jenkinson, D. H.: Blockade by WB4101 of α-adrenoceptors in the rat vas deferens and guinea-pig taenia caeci. Eur. J. Pharmacol. 52, 303–311 (1978)

    Google Scholar 

  • Cedarbaum, J. M., Aghajanian, G. K.: Catecholamine receptors on locus coeruleus neurons: pharmacological characterization. Eur. J. Pharmacol. 44, 375–385 (1977)

    Google Scholar 

  • Constantine, J. W., Weeks, R. A., McShane, W. K.: Prazosin and presynaptic α-receptors in the cardioaccelerator nerve of the dog. Eur. J. Pharmacol. 50, 51–60 (1978)

    Google Scholar 

  • Diem, K., Lentner, C. (eds.) Documenta Geigy. Wissenschaftliche Tabellen. Basel: Geigy 1968.

    Google Scholar 

  • Doxey, J. C.: Pre- and postsynaptic effects of α-agonists in the anococcygeus muscle of the pithed rat. Eur. J. Pharmacol. 54, 185–189 (1979)

    Google Scholar 

  • Drew, G. M.: Pharmacological characterisation of the presynaptic α-adrenoceptor in the rat vas deferens. Eur. J. Pharmacol. 42, 123–130 (1977)

    Google Scholar 

  • Drew, G. M.: Pharmacological characterization of the presynaptic α-adrenoceptors regulating cholinergic activity in the guinea-pig ileum. Br. J. Pharmacol. 64, 293–300 (1978)

    Google Scholar 

  • Dubocovich, M. L., Langer, S. Z.: Negative feed-back regulation of noradrenaline release by nerve stimulation in the perfused cat's spleen: differences in potency of phenoxybenzamine in blocking the pre- and post-synaptic adrenergic receptors. J. Physiol. (Lond.) 237, 505–519 (1974)

    Google Scholar 

  • 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 

  • Furchgott, R. F.: The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In: Catecholamines (H. Blaschko and E. Muscholl, eds.), pp. 283–335. Berlin, Heidelberg, New York: Springer 1972

    Google Scholar 

  • Graefe, K. H., Stefano, F. J. E., Langer, S. Z.: Preterential metabolism of (-)-3H-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem. Pharmacol. 22, 1147–1160 (1973)

    Google Scholar 

  • Hesse, E.: Indolalkaloide in Tabellen. Berlin, Göttingen, Heidelberg: Springer 1964

    Google Scholar 

  • Kapur, H., Mottram, D. R.: A comparative study on the pre- and post-synaptic alpha blocking activity of a series of benzodioxanes. Biochem. Pharmacol. 27, 1879–1880 (1978)

    Google Scholar 

  • Kohli, J. D., Balwani, J. H., Ray, C., De, N. N.: Pharmacological action of rauwolscine: Part I — Adrenergic blocking activity. Arch. Int. Pharmacodyn. 111, 108–121 (1957)

    Google Scholar 

  • Lambert, G. A., Lang, W. J.: Interaction between yohimbine alkaloids and amphetamine in mice. Psychopharmacology 51, 209–212 (1977)

    Google Scholar 

  • Lambert, G. A., Lang, W. J., Friedman, E., Meller, E., Gershon, S.: Pharmacological and biochemical properties of isomeric yohimbine alkaloids. Eur. J. Pharmacol. 49, 39–48 (1978)

    Google Scholar 

  • Langer, S. Z.: The regulation of transmitter release elicited by nerve stimulation through a presynaptic feed-back mechanism. In: Frontiers in catecholamine research (E. Usdin and S. H. Snyder, eds.), pp. 543–549. New York: Pergamon 1973

    Google Scholar 

  • Langer, S. Z.: Presynaptic regulation of catecholamine release. Biochem. Pharmacol. 23, 1793–1800 (1974)

    Google Scholar 

  • Lasch, P., Jakobs, K. H.: Agonistic and antagonistic effects of various α-adrenergic agonists in human platelets. Naunyn-Schmeideberg's Arch. Pharmacol. 306, 119–125 (1979)

    Google Scholar 

  • Marshall, I., Nasmyth, P. A., Nicholl, C. G., Shepperson, N. B.: α-Adrenoceptors in the mouse vas deferens and their effects on its response to electrical stimulation. Br. J. Pharmacol. 62, 147–151 (1978)

    Google Scholar 

  • Morrison, G. A.: Conformational analysis of some alkaloids. Fortschr. Chem Organ. Naturstoffe 25, 269–317 (1967)

    Google Scholar 

  • Nickerson, M.: The pharmacology of adrenergic blockade. Pharmacol. Rev. 1, 27–101 (1949)

    Google Scholar 

  • Papeschi, R., Sourkes, T. L., Youdim, M. B. H.: The effect of yohimbine on brain serotonin metabolism, motor behavior and body temperature of the rat. Eur. J. Pharmacol. 15, 318–326 (1971)

    Google Scholar 

  • Schrold, J., Nedergaard, O. A.: Effect of propylene glycol and ethanol on 3H-noradrenaline efflux from an isolated blood vessel. Experientia 33, 1208–1209 (1977)

    Google Scholar 

  • Starke, K.: Alpha sympathomimetic inhibition of adrenergic and cholinergic transmission in the rabbit heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 274, 18–45 (1972)

    Google Scholar 

  • Starke, K., Altmann, K. P.: Inhibition of adrenergic neurotransmission by clonidine: an action on prejunctional α-receptors. Neuropharmacology 12, 339–347 (1973)

    Google Scholar 

  • Starke, K., Langer, S. Z.: A note on terminology for presynaptic receptors. In: Presynaptic receptors (S. Z. Langer, K. Starke and M. L. Dubocovich, eds.). Oxford: Pergamon 1979 (in press)

    Google Scholar 

  • Starke, K., Montel, H., Gayk, W., Merker, R.: Comparison of the effects of clonidine on pre- and postsynaptic adrenoceptors in the rabbit pulmonary artery. α-sympathomimetic inhibition of neurogenic vasoconstriction. Naunyn-Schmiedeberg's Arch. Pharmacol. 285, 133–150 (1974)

    Google Scholar 

  • Starke, K., Borowski, E., Endo, T.: Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Eur. J. Pharmacol. 34, 385–388 (1975a)

    Google Scholar 

  • Starke, K., Endo, T., Taube, H. D.: Relative pre- and postsynaptic potencies of α-adrenoceptor agonists in the rabbit pulmonary artery. Naunyn-Schmiedeberg's Arch. Pharmacol. 291, 55–78 (1975b)

    Google Scholar 

  • Su, C., Bevan, J. A.: The release of H3-norepinephrine in arterial strips studied by the technique of superfusion and transmural stimulation. J. Pharmacol. Exp. Ther. 172, 62–68 (1970)

    Google Scholar 

  • Tanaka, T., Weitzell, R., Starke, K.: High selectivity of rauwolscine for presynaptic α-adrenoceptors. Eur. J. Pharmacol. 52, 239–240 (1978)

    Google Scholar 

  • Weitzell, R., Tanaka, T., Starke, K.: Pre- and postsynaptic α-adrenolytic effects of yohimbine stereoisomers. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, R58 (1979)

    Google Scholar 

  • Wikberg, J.: Differentiation between pre- and postjunctional α-receptors in guinea pig ileum and rabbit aorta. Acta Physiol. Scand. 103, 225–239 (1978)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmakologisches Institut, Hermann-Herder-Strasse 5, D-7800, Freiburg i. Br., Germany

    Rudolf Weitzell, Toshiyuki Tanaka & Klaus Starke

Authors
  1. Rudolf Weitzell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshiyuki Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Klaus Starke
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weitzell, R., Tanaka, T. & Starke, K. Pre- and postsynaptic effects of yohimbine stereoisomers on noradrenergic transmission in the pulmonary artery of the rabbit. Naunyn-Schmiedeberg's Arch. Pharmacol. 308, 127–136 (1979). https://doi.org/10.1007/BF00499054

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00499054

Key words

Search

Navigation