Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 299, Issue 3, pp 289–294 | Cite as

Influence of changed calcium and potassium concentration on the algesic effect of bradykinin and acetylcholine

  • F. Lembeck
  • H. Juan
Article

Summary

  1. 1.

    In the isolated perfused rabbit ear bradykinin (B) and acetylcholine (ACh) stimulate paravascular pain receptors. Changed calcium (Ca2+) and potassium (K+) concentrations were used to investigate whether there were different “pharmacological” receptors for B and ACh.

     
  2. 2.

    Increased [K+] (26.8 mM) lowered the pain threshold for both B and ACh. Decreased [K+] (0.27 mM) did not alter the algesic effect of B or ACh.

     
  3. 3.

    Increased [Ca2+] (3.6 and 9.0 mM) strongly enhanced the algesic effect of ACh but reduced that of B. Decreased [Ca2+] (0.18 and 0.6 mM) also reduced the algesic effect of B but did not influence that of ACh. Single i.a. injections of CaCl2 (1–5 mg) directly stimulated paravascular pain receptors.

     
  4. 4.

    Prostaglandin E1 (PGE1, 10 ng/ml) reversed the inhibitory influence of 9 mM [Ca2+] on the B effect and further enhanced the Ca2+-facilitated ACh effect.

     
  5. 5.

    Conclusion. ACh and B exert their algesic effect via different receptor sites. This was concluded from the use of changed [Ca2+] and [K+]. High [K+] increased the effect of B and ACh due to membrane depolarization. Low [Ca2+] diminished only the effect of B but not that of ACh. High [Ca2+] increased the algesic effect of ACh possibly due to an enhanced Ca2+ influx at the generator region thus contributing to excitation. This finding is substantiated by the fact that Ca2+ by itself in sufficiently high amounts can stimulate pain receptors. High [Ca2+] reduced the effect of B by interfering with the pain enhancing action of PGE released by B, the algesic effect of which being strongly dependent on the presence of PGE.

     

An interference of high [Ca2+] with the direct effect of B is rather unlikely since during inhibited PGE-release high [Ca2+] no longer reduces significantly the effect of B.

Key words

Bradykinin Acetylcholine Calcium Potassium Prostaglandin E1 Pain receptors 

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References

  1. Benjamin, F. B.: Release of intracellular potassium as the physiological stimulus for pain. Fed. Proc. 18, 10 (1959)Google Scholar
  2. Brink, F., Bronk, D. W., Larrabee, M. G.: Chemical excitation of nerve. Ann. N. Y. Acad. Sci. 47, 457–485 (1946)Google Scholar
  3. Douglas, W. W., Poisner, A. M.: On the mode of action of acetylcholine in evoking adrenal medullary secretion: Increased uptake of calcium during the secretory response. J. Physiol. (Lond.) 162, 385–392 (1962)Google Scholar
  4. Eagling, E. M., Lovell, H. G., Pickles, V. R.: Interaction of prostaglandin E1 and calcium in the guinea-pig myometrium. Br. J. Pharmacol. 44, 510–516 (1972)Google Scholar
  5. Ferreira, S. H., Moncada, S., Vane, J. R.: Prostaglandins and the mechanism of analgesia produced by aspirin-like drugs. Br. J. Pharmacol. 49, 86–97 (1973)Google Scholar
  6. Ferreira, S. H., Moncada, S., Vane, J. R.: Potentiation by prostaglandins of the nociceptive activity of bradykinin in the dog knee joint. Br. J. Pharmacol. 50, 461P (1974)Google Scholar
  7. Ginzel, K. H.: The importance of sensory nerve endings as sites of drug action. Naunyn-Schmiedeberg's Arch. Pharmacol. 288, 29–56 (1975)Google Scholar
  8. Hadházy, P., Todorov, S., Nador, T.: Antagonism by Ca2+ of the inhibitory action of PGE1 on the electrically induced vasoconstriction in the rabbit ear artery. Eur. J. Pharmacol. 34, 393–395 (1975)Google Scholar
  9. Hedqvist, P.: Antagonism by calcium of the inhibitory action of prostaglandin E2 on sympathetic neurotransmission in the cat spleen. Acta Physiol. Scand. 80, 269–275 (1970)Google Scholar
  10. Johnson, D. G., Thoa, N. B., Weinshilboum, R., Axelrod, J., Kopin, I. J.: Enhanced release of dopamine β-hydroxylase from sympathetic nerves by calcium and phenoxybenzamine and its reversal by prostaglandins. Proc. Natl. Acad. Sci. U.S.A. 68, 2227–2230 (1971)Google Scholar
  11. Juan, H., Lembeck, F.: Influence of prostaglandin E1, indomethacin, calcium and potassium on the action of nociceptive substances. Naunyn-Schmiedeberg's Arch. Pharmacol. 282, R42 (1974a)Google Scholar
  12. Juan, H., Lembeck, F.: Action of peptides and other algesic agents on paravascular pain receptors of the isolated perfused rabbit ear. Naunyn-Schmiedeberg's Arch. Pharmacol. 283, 151–164 (1974b)Google Scholar
  13. Juan, H., Lembeck, F.: Inhibition of the action of bradykinin and acetylcholine on paravascular pain receptors by tetrodotoxin and procaine. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 389–395 (1975)Google Scholar
  14. Juan, H., Lembeck, F.: Release of prostaglandins from the isolated perfused rabbit ear by bradykinin and acetylcholine. Agents and Actions, 6, 642–645 (1976)Google Scholar
  15. Kanno, M., Dunning, B. B., Machne, X.: Calcium dependence of acetylcholine induced conductance changes. Life Sci. 18, 311–318 (1976)Google Scholar
  16. Lembeck, F.: Untersuchungen über die Auslösung afferenter Impulse. Naunyn-Schmiedebergs Arch. Exp. Path. Pharmak. 230, 1–9 (1957)Google Scholar
  17. Lembeck, F., Juan, H.: Interaction of prostaglandins and indomethacin with algesic substances. Naunyn-Schmiedeberg's Arch. Pharmacol. 285, 301–313 (1974)Google Scholar
  18. Lembeck, F., Popper, H., Juan, H.: Release of prostaglandins by bradykinin as an intrinsic mechanism of its algesic effect. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, 69–73 (1976)Google Scholar
  19. Lim, R. K. S.: A revised concept of the mechanism of analgesia and pain. In: R. S. Knighton and P. R. Dumke: Pain, pp. 117–154. Boston: Little Brown 1966Google Scholar
  20. Magazanik, L. G., Vyskocil, F.: Dependence of acetylcholine desensitization on the membrane potential of frog muscle fibre and the ionic changes in the medium. J. Physiol. (Lond.) 210, 507–518 (1970)Google Scholar
  21. McGiff, J. C., Terragno, N. A., Malik, K. U., Lonigro, A. J.: Release of prostaglandin E-like substance from canine kidney by bradykinin. Circ. Res. 31, 36–43 (1972)Google Scholar
  22. Moncada, S., Ferreira, S. H., Vane, J. R.: Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirinlike drugs in the dog knee joint. Eur. J. Pharmacol. 31, 250–260 (1975)Google Scholar
  23. Paintal, A. S.: Effect of drugs on vertebrate mechanoreceptors. Pharmacol. Rev. 16, 341–380 (1964)Google Scholar
  24. Palmer, M. A., Piper, P. J., Vane, J. R.: Release of rabbit aorta contracting substance (RCS) and prostaglandins induced by chemical or mechanical stimulation of guinea-pig lungs. Br. J. Pharmacol. 49, 226–242 (1973)Google Scholar
  25. Parsons, R. L., Cochrane, D. E., Schnitzler, R. M.: End-plate desensitization: specifity of calcium. Life Sci. 13, 459–465 (1973)Google Scholar
  26. Schreiner, H. J.: Das Wärmegefühl nach Calciuminjektionen. Inaug-Diss., Göttingen 1936Google Scholar
  27. Stjärne, L.: Kinetics of secretion of sympathetic neurotransmitter as a function of external calcium: mechanism of inhibitory effect of prostaglandin E. Acta Physiol. Scand. 87, 428–430 (1973)Google Scholar
  28. Takeuchi, N.: Effects of calcium on the conductance change of the end-plate membrane during the action of transmitter. J. Physiol. (Lond.) 167, 141–155 (1963)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • F. Lembeck
    • 1
  • H. Juan
    • 1
  1. 1.Institut für Experimentelle und Klinische Pharmakologie der Universität GrazGrazAustria

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