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Possible feed-back inhibition of noradrenaline release by purine compounds

  • María A. Enero
  • B. Q. Saidman
Article

Summary

The contractile responses to transmural stimulation of, and the overflow of tritium from the rat portal vein prelabelled with 3H-noradrenaline were studied.

The contractile responses of the rat portal vein were sustained throughout the period of stimulation. The tension developed did not decline when two consecutive periods of stimulation were compared. In contrast, the tritium overflow decreased during the second period of stimulation.

Preincubation with 3 μM phenoxybenzamine during 30 min increased 3-fold the tritium overflow during stimulation.

Phentolamine and phenoxybenzamine were nearly equipotent in reducing the vascular response to stimulation. In contrast, phentolamine was less potent than phenoxybenzamine in increasing the 3H-noradrenaline overflow elicited by stimulation.

The results obtained with phentolamine are interpreted in terms of a different potency of phentolamine to produce blockade of prejunctional and postjunctional α-adrenoceptors in the rat portal vein.

ATP inhibited by 70% the tritium overflow induced by stimulation. The potency of ATP in inhibiting the overflow increased when the prejunctional α-adrenoceptors were blocked.

The purine compounds ATP, ADP, AMP and adenosine were roughly equipotent in inhibiting stimulation-induced tritium overflow. The tritium released by stimulation decreased when uptake and metabolism of adenosine were inhibited. Under physiological conditions, a prejunctional purinergic inhibition of noradrenaline release might be involved in an endogenously mediated negative feed-back regulatory mechanism. It is possible that the purinergic inhibition of the noradrenaline liberation elicited by stimulation plays a physiological role in tissues with both purinergic and adrenergic innervation.

Key words

Transmural stimulation Noradrenaline Purine compounds Portal vein Neurotransmission Adenosine receptors 

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References

  1. Adler-Graschinsky, E., Langer, S. Z.: Possible role of a β-adrenoceptor in the regulation of noradrenaline release by nerve stimulation through a positive feed-back mechanism. Brit. J. Pharmacol. 53, 43–50 (1975)Google Scholar
  2. Avakian, O. V., Gillespie, J. S.: Uptake of noradrenaline by adrenergic nerves, smooth-muscle and connective tissue in isolated perfused arteries and its correlation with the vasoconstrictor response. Brit. J. Pharmacol. 32, 168–184 (1968)Google Scholar
  3. Ballard, D. R., Abboud, F. M., Mayer, H. E.: Release of a humoral vasodilator substance during neurogenic vasodilatation. Amer. J. Physiol 219, 1451–1457 (1970)Google Scholar
  4. Beck, L., Brody, M. J.: Physiology of vasodilatation. Angiology 12, 202–222 (1961)Google Scholar
  5. Burnstock, G.: Purinergic nerves. Pharmacol. Rev. 24, 509–581 (1972)Google Scholar
  6. Campbell, G.: Autonomic nervous supply to effector tissues. In: Smooth muscle (E. Bülbring, A. F. Brading, A. W. Jones and T. Tomita, eds.), pp. 451–495. London: E. Arnold (Publishers) Ltd. 1970Google Scholar
  7. Draskóczy, P. R., Trendelenburg, U.: Intraneuronal and extraneuronal accumulation of sympathomimetic amines in the isolated nictitating membrane of the cat. J. Pharmacol. exp. Ther. 174, 290–306 (1970)Google Scholar
  8. 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 pre-and postsynaptic adrenergic receptors. J. Physiol. (Lond.) 237, 505–519 (1974)Google Scholar
  9. Dubocovich, M. L., Langer, S. Z.: Evidence against a physiological role of prostaglandins in the regulation of noradrenaline release in the cat spleen. J. Physiol. (Lond.) 251, 737–762 (1975)Google Scholar
  10. Enero, M. A., Langer, S. Z.: Influence of reserpine-induced depletion of noradrenaline on the negative feed-back mechanism for transmitter release during nerve stimulation. Brit. J. Pharmacol. 49, 214–225 (1973)Google Scholar
  11. Enero, M. A., Langer, S. Z.: Inhibition by dopamine of 3H-noradrenaline release elicited by nerve stimulation in the isolated cat's nictitating membrane. Naunyn-Schmiedeberg's Arch. Pharmacol. 289, 179–203 (1975)Google Scholar
  12. Enero, M. A., Langer, S. Z., Rothlin, R. P., Stefano, F. J. E.: Role of the α-adrenoceptor in regulating noradrenaline overflow by nerve stimulation. Brit. J. Pharmacol. 44, 672–688 (1972)Google Scholar
  13. Farah, M. B., Adler-Graschinsky, E., Langer, S. Z.: Liberación de 3H-noradrenalina pro K+ en hipotálamo de rata: secuencia metabólica y mecanismos regulatorios. Medicina XXXIII, 599–600 (1973)Google Scholar
  14. Farah, M. B., Langer, S. Z., Protection by phentolamine against the effects of phenoxybenzamine on transmitter release elicited by nerve stimulation in the perfused cat heart. Brit. J. Pharmacol. 52, 549–557 (1974)Google Scholar
  15. Farnebo, L. O., Hamberger, B.: Drug-induced changes in the release of 3H-nordarenaline from field stimulated rat iris Brit. J. Pharmacol. 43, 97–106 (1971a)Google Scholar
  16. Farnebo, L. O., Hamberger, B.: Drug-induced changes in the release of 3H-monoamines from field stimulated rat brain slices. Acta physiol. scand., Suppl. 371, 35–44 (1971b)Google Scholar
  17. Farnebo, L. O., Hamberger, B.: Catecholamine release and receptors in brain slices. In: Frontiers in catecholamine research (E. Usdin and S. Snyder, eds.), pp. 589–593. New York: Pergamon Press 1973Google Scholar
  18. Frame, M. H., Hedqvist, P.: Evidence for prostaglandin mediated prejunctional control of renal sympathetic transmitter release and vascular tone. Brit. J. Pharmacol. 54, 189–196 (1975)Google Scholar
  19. Fredholm, B. B.: Vascular and metabolic effects of theophylline, dibutyryl cyclic AMP and dibutyryl cyclic GMP in canine subcutaneous adipose tissue in situ. Acta physiol. scand. 90, 226–236 (1974)Google Scholar
  20. Geffen, L. B., Livett, B. G.: Synaptic vesicles in sympathetic neurons. Physiol. Rev. 51, 98–157 (1971)Google Scholar
  21. Graham, B. H., Lioy, F.: Histaminergic vasodilatation in the hindlimb of the dog. Pflügers Arch. 342, 307–318 (1973)Google Scholar
  22. Häggendal, J., Johansson, B., Jjung, B.: Correlation between noradrenaline release and effector response to nerve stimulation in the rat portal vein in vitro. Acta physiol. scand., Suppl. 349, 17–32 (1970)Google Scholar
  23. Häggendal, J., Johansson, B., Jonason, J., Ljung, B.: Effects of phenoxybenzamine on transmitter release and effector response in the isolated portal vein. J. Pharm. Pharmacol. 24, 161–164 (1972)Google Scholar
  24. Hedqvist, P., Fredholm, B. B.: Effects of adenosine on adrenergic neurotransmission; prejunctional inhibition and postjunctional enhancement. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 217–223 (1976)Google Scholar
  25. Hertting, G., Axelrod, J., Whitby, L. G.: Effects of drugs on the uptake and metabolism of 3H-norpinephrine. J. Pharmacol. exp. Ther. 134, 146–153 (1961)Google Scholar
  26. Hughes, J., Kosterlitz, H. W., Leslie, F. M.: Effects of morphine on adrenergic transmission in the mouse vas deferens. Assessment of agonist and antagonist potencies of narcotic analgesics. Brit. J. Pharmacol. 53, 371–381 (1975)Google Scholar
  27. Hughes, J., Vane, J. R.: An analysis of the responses of the isolated portal vein of the rabbit to electrical stimulation and to drugs. Brit. J. Pharmacol. 30, 46–66 (1967)Google Scholar
  28. Hughes, J., Vane, J. R.: Relaxations of the isolated portal vein of the rabbit induced by nicotine and electrical stimulation. Brit. J. Pharmacol. 39, 476–489 (1970)Google Scholar
  29. Iversen, L. L.: The uptake and storage of noradrenaline in sympathetic nerves, pp 147. London: Cambridge University Press 1967Google Scholar
  30. Kirpekar, S. M., Puig, M.: Effect of flow stop on noradrenaline release from normal spleens and spleens treated with cocaine, phentolamine or phenoxybenzamine. Brit. J. Pharmacol. 43, 359–369 (1971)Google Scholar
  31. Lagercrantz, H., Sjärne, L.: Evidence that most noradrenaline is stored without ATP in sympathetic large dense core nerve vesicles. Nature (Lond.) 249, 843–844 (1974)Google Scholar
  32. 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. Snyder, eds.), pp. 543–549. New York: Pergamon Press 1973Google Scholar
  33. Langer, S. Z.: Presynaptic regulation of catecholamine release. Biochem. Pharmacol. 23, 1793–1800 (1974)Google Scholar
  34. Langer, S. Z., Adler, E., Enero, M. A., Stefano, F. J. E.: The role of the α-receptor in regulating noradrenaline overflow by nerve stimulation. XXVth Int. Congr. Physiol. Sciences, p. 335, Munich 1971Google Scholar
  35. Langer, S. Z., Enero, M. A., Adler-Graschinsky, E., Dubocovich, M. L., Celuchi, S. M.: Presynaptic regulatory mechanism for noradrenaline release by nerve stimulation. Central action of drugs in blood pressure regulation (D. S. Davies and J. L. Reid, eds.), pp. 133–150. London: Pitman Medical Publishing Co. Ltd. 1975Google Scholar
  36. Paton, W. D. M., Vizi, E. S.: The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip. Brit. J. Pharmacol. 35, 10–28 (1969)Google Scholar
  37. Sawynok, J., Jhamandas, K. H.: Inhibition of acetylcholine release from cholinergic nerves by adenosine, adenine nucleotides and morphine: Antagonism by theophylline. J. Pharmacol. exp. Ther. 197, 379–390 (1976)Google Scholar
  38. Sjöberg, B., Wahlström, B. A.: The effect of ATP and related compounds on spontaneous mechanical activity in the rat portal vein. Acta physiol. scand. 94, 46–53 (1975)Google Scholar
  39. Snedecor, G. W., Cochran, W. G.: Statistical methods, 6th Ed. Ames: The Iowa State University Press 1969Google Scholar
  40. Starke, K.: Influence of α-receptor stimulants on noradrenaline release. Naturwissenschaften 58, 420 (1971)Google Scholar
  41. 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
  42. Starke, K., Montel, H.: Alpha receptor mediated modulation of transmitter release from central noradrenergic neurones. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 53–60 (1973)Google Scholar
  43. 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 (1975)Google Scholar
  44. Stjärne, L.: Inhibitory effect of prostaglandin E2 on noradrenaline secretion from sympathetic nerves as a function of external calcium. Prostaglandins 3, 105–109 (1973)Google Scholar
  45. Su, C.: Vasodilator action of adenine comoounds on the rabbit portal vein. Pharmacologist 16, 289 (1974)Google Scholar
  46. Su, C.: Neurogenic release of purine compounds in blood vessels. J. Pharmacol. exp. Ther. 195, 159–166 (1975)Google Scholar
  47. Su, C., Bevan, J. A.: Neurogenic release of adenine compounds in blood vessels. Fed. Proc. 33, 583 (1974)Google Scholar
  48. Su, C., Bevan, J. A., Burnstock, G.: Release of 3H-ATP during stimulation of enteric nerves. Science 173, 336–339 (1971)Google Scholar
  49. Uvnäs, B.: Sympathetic vasodilator outflow. Physiol. Rev. 34, 608–618 (1954)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • María A. Enero
    • 1
  • B. Q. Saidman
    • 1
  1. 1.Instituto de Investigaciones FarmacológicasConsejo Nacional de Investigaciones Cientificas y TécnicasBuenos AiresArgentina

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