Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Jan;108(1):185–190. doi: 10.1111/j.1476-5381.1993.tb13460.x

Effect of bradykinin and prostaglandins on the release of calcitonin gene-related peptide-like immunoreactivity from the rat spinal cord in vitro.

L Andreeva 1, H P Rang 1
PMCID: PMC1907723  PMID: 7679028

Abstract

1. The release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) from the dorsal horn of the rat spinal cord in vitro in response to dorsal root stimulation was measured by radioimmunoassay. 2. Stimulation of the dorsal roots (3 or 4 roots on each side) at 10 Hz for 5 min evoked a mean release (R1) of 134.3 +/- 17.5 (n = 10) fmol CGRP-LI; the release (R2) evoked by a second stimulation period 30 min later under control conditions was 77 +/- 10% (n = 10) of R1. Test compounds were applied to the preparation following release R1, and their effect calculated from the value of R2/R1. 3. Bradykinin (0.01-10 microM) had no significant effect on the basal release of CGRP-LI, but at 0.1-10 microM it increased 2-3 fold the release evoked by dorsal root stimulation. 4. This effect of bradykinin was prevented by indomethacin (10 microM), or by the B2-receptor antagonist, Hoe140 (1-10 microM). In the presence of Hoe140, bradykinin significantly reduced R2/R1; the explanation for this is not clear. 5. The B1-receptor agonist, Des-Arg9-bradykinin (10 microM), did not affect CGRP-LI release nor was the effect of bradykinin blocked by the B1-receptor antagonist, Des-Arg9-Leu8-bradykinin (10 microM). 6. Various prostaglandins were found to mimic the effect of bradykinin on CGRP-LI release. Their approximate order of potency was prostaglandin D2 (PGD2) = PGE1 > PGF2 alpha = PGE2; PGI2 was ineffective at 10 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
185

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amann R., Donnerer J., Lembeck F. Ruthenium red selectively inhibits capsaicin-induced release of calcitonin gene-related peptide from the isolated perfused guinea pig lung. Neurosci Lett. 1989 Jul 3;101(3):311–315. doi: 10.1016/0304-3940(89)90551-x. [DOI] [PubMed] [Google Scholar]
  2. Bareis D. L., Manganiello V. C., Hirata F., Vaughan M., Axelrod J. Bradykinin stimulates phospholipid methylation, calcium influx, prostaglandin formation, and cAMP accumulation in human fibroblasts. Proc Natl Acad Sci U S A. 1983 May;80(9):2514–2518. doi: 10.1073/pnas.80.9.2514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boland L. M., Allen A. C., Dingledine R. Inhibition by bradykinin of voltage-activated barium current in a rat dorsal root ganglion cell line: role of protein kinase C. J Neurosci. 1991 Apr;11(4):1140–1149. doi: 10.1523/JNEUROSCI.11-04-01140.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Braas K. M., Manning D. C., Perry D. C., Snyder S. H. Bradykinin analogues: differential agonist and antagonist activities suggesting multiple receptors. Br J Pharmacol. 1988 May;94(1):3–5. doi: 10.1111/j.1476-5381.1988.tb11492.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burgess G. M., Mullaney I., McNeill M., Coote P. R., Minhas A., Wood J. N. Activation of guanylate cyclase by bradykinin in rat sensory neurones is mediated by calcium influx: possible role of the increase in cyclic GMP. J Neurochem. 1989 Oct;53(4):1212–1218. doi: 10.1111/j.1471-4159.1989.tb07417.x. [DOI] [PubMed] [Google Scholar]
  6. Burgess G. M., Mullaney I., McNeill M., Dunn P. M., Rang H. P. Second messengers involved in the mechanism of action of bradykinin in sensory neurons in culture. J Neurosci. 1989 Sep;9(9):3314–3325. doi: 10.1523/JNEUROSCI.09-09-03314.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chung K., Lee W. T., Carlton S. M. The effects of dorsal rhizotomy and spinal cord isolation on calcitonin gene-related peptide-labeled terminals in the rat lumbar dorsal horn. Neurosci Lett. 1988 Jul 19;90(1-2):27–32. doi: 10.1016/0304-3940(88)90781-1. [DOI] [PubMed] [Google Scholar]
  8. Coleridge H. M., Coleridge J. C., Ginzel K. H., Baker D. G., Banzett R. B., Morrison M. A. Stimulation of 'irritant' receptors and afferent C-fibres in the lungs by prostaglandins. Nature. 1976 Dec 2;264(5585):451–453. doi: 10.1038/264451a0. [DOI] [PubMed] [Google Scholar]
  9. Corrêa F. M., Innis R. B., Uhl G. R., Snyder S. H. Bradykinin-like immunoreactive neuronal systems localized histochemically in rat brain. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1489–1493. doi: 10.1073/pnas.76.3.1489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dolphin A. C., McGuirk S. M., Scott R. H. An investigation into the mechanisms of inhibition of calcium channel currents in cultured sensory neurones of the rat by guanine nucleotide analogues and (-)-baclofen. Br J Pharmacol. 1989 May;97(1):263–273. doi: 10.1111/j.1476-5381.1989.tb11950.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dray A., Bettaney J., Forster P., Perkins M. N. Activation of a bradykinin receptor in peripheral nerve and spinal cord in the neonatal rat in vitro. Br J Pharmacol. 1988 Dec;95(4):1008–1010. doi: 10.1111/j.1476-5381.1988.tb11732.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dunn P. M., Rang H. P. Bradykinin-induced depolarization of primary afferent nerve terminals in the neonatal rat spinal cord in vitro. Br J Pharmacol. 1990 Jul;100(3):656–660. doi: 10.1111/j.1476-5381.1990.tb15863.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ewald D. A., Pang I. H., Sternweis P. C., Miller R. J. Differential G protein-mediated coupling of neurotransmitter receptors to Ca2+ channels in rat dorsal root ganglion neurons in vitro. Neuron. 1989 Feb;2(2):1185–1193. doi: 10.1016/0896-6273(89)90185-2. [DOI] [PubMed] [Google Scholar]
  14. Franco-Cereceda A., Saria A., Lundberg J. M. Differential release of calcitonin gene-related peptide and neuropeptide Y from the isolated heart by capsaicin, ischaemia, nicotine, bradykinin and ouabain. Acta Physiol Scand. 1989 Feb;135(2):173–187. doi: 10.1111/j.1748-1716.1989.tb08565.x. [DOI] [PubMed] [Google Scholar]
  15. Fujiwara Y., Mantione C. R., Yamamura H. I. Identification of B2 bradykinin binding sites in guinea-pig brain. Eur J Pharmacol. 1988 Mar 15;147(3):487–488. doi: 10.1016/0014-2999(88)90187-2. [DOI] [PubMed] [Google Scholar]
  16. Gammon C. M., Allen A. C., Morell P. Bradykinin stimulates phosphoinositide hydrolysis and mobilization of arachidonic acid in dorsal root ganglion neurons. J Neurochem. 1989 Jul;53(1):95–101. doi: 10.1111/j.1471-4159.1989.tb07299.x. [DOI] [PubMed] [Google Scholar]
  17. Geppetti P., Del Bianco E., Santicioli P., Lippe I. T., Maggi C. A., Sicuteri F. Release of sensory neuropeptides from dural venous sinuses of guinea pig. Brain Res. 1990 Feb 26;510(1):58–62. doi: 10.1016/0006-8993(90)90727-s. [DOI] [PubMed] [Google Scholar]
  18. Geppetti P., Del Bianco E., Tramontana M., Vigano T., Folco G. C., Maggi C. A., Manzini S., Fanciullacci M. Arachidonic acid and bradykinin share a common pathway to release neuropeptide from capsaicin-sensitive sensory nerve fibers of the guinea pig heart. J Pharmacol Exp Ther. 1991 Nov;259(2):759–765. [PubMed] [Google Scholar]
  19. Geppetti P., Patacchini R., Cecconi R., Tramontana M., Meini S., Romani A., Nardi M., Maggi C. A. Effects of capsaicin, tachykinins, calcitonin gene-related peptide and bradykinin in the pig iris sphincter muscle. Naunyn Schmiedebergs Arch Pharmacol. 1990 Apr;341(4):301–307. doi: 10.1007/BF00180655. [DOI] [PubMed] [Google Scholar]
  20. Gross R. A., Macdonald R. L. Cyclic AMP selectively reduces the N-type calcium current component of mouse sensory neurons in culture by enhancing inactivation. J Neurophysiol. 1989 Jan;61(1):97–105. doi: 10.1152/jn.1989.61.1.97. [DOI] [PubMed] [Google Scholar]
  21. Halushka P. V., Mais D. E., Mayeux P. R., Morinelli T. A. Thromboxane, prostaglandin and leukotriene receptors. Annu Rev Pharmacol Toxicol. 1989;29:213–239. doi: 10.1146/annurev.pa.29.040189.001241. [DOI] [PubMed] [Google Scholar]
  22. Hock F. J., Wirth K., Albus U., Linz W., Gerhards H. J., Wiemer G., Henke S., Breipohl G., König W., Knolle J. Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies. Br J Pharmacol. 1991 Mar;102(3):769–773. doi: 10.1111/j.1476-5381.1991.tb12248.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Holzer P., Peskar B. M., Peskar B. A., Amann R. Release of calcitonin gene-related peptide induced by capsaicin in the vascularly perfused rat stomach. Neurosci Lett. 1990 Jan 1;108(1-2):195–200. doi: 10.1016/0304-3940(90)90730-w. [DOI] [PubMed] [Google Scholar]
  24. Juan H., Lembeck F. Action of peptides and other algesic agents on paravascular pain receptors of the isolated perfused rabbit ear. Naunyn Schmiedebergs Arch Pharmacol. 1974;283(2):151–164. doi: 10.1007/BF00501142. [DOI] [PubMed] [Google Scholar]
  25. Kuraishi Y., Nanayama T., Ohno H., Minami M., Satoh M. Antinociception induced in rats by intrathecal administration of antiserum against calcitonin gene-related peptide. Neurosci Lett. 1988 Oct 17;92(3):325–329. doi: 10.1016/0304-3940(88)90611-8. [DOI] [PubMed] [Google Scholar]
  26. Laneuville O., Reader T. A., Couture R. Intrathecal bradykinin acts presynaptically on spinal noradrenergic terminals to produce antinociception in the rat. Eur J Pharmacol. 1989 Jan 17;159(3):273–283. doi: 10.1016/0014-2999(89)90158-1. [DOI] [PubMed] [Google Scholar]
  27. Lembeck F., Popper H., Juan H. Release of prostaglandins by bradykinin as an intrinsic mechanism of its algesic effect. Naunyn Schmiedebergs Arch Pharmacol. 1976 Jul;294(1):69–73. doi: 10.1007/BF00692786. [DOI] [PubMed] [Google Scholar]
  28. Longhurst J. C., Dittman L. E. Hypoxia, bradykinin, and prostaglandins stimulate ischemically sensitive visceral afferents. Am J Physiol. 1987 Sep;253(3 Pt 2):H556–H567. doi: 10.1152/ajpheart.1987.253.3.H556. [DOI] [PubMed] [Google Scholar]
  29. Lou Y. P., Franco-Cereceda A., Lundberg J. M. Omega-conotoxin inhibits CGRP release and bronchoconstriction evoked by a low concentration of capsaicin. Acta Physiol Scand. 1991 Jan;141(1):135–136. doi: 10.1111/j.1748-1716.1991.tb09057.x. [DOI] [PubMed] [Google Scholar]
  30. Manzini S., Perretti F., De Benedetti L., Pradelles P., Maggi C. A., Geppetti P. A comparison of bradykinin- and capsaicin-induced myocardial and coronary effects in isolated perfused heart of guinea-pig: involvement of substance P and calcitonin gene-related peptide release. Br J Pharmacol. 1989 Jun;97(2):303–312. doi: 10.1111/j.1476-5381.1989.tb11955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mapp C. E., Fabbri L. M., Boniotti A., Maggi C. A. Prostacyclin activates tachykinin release from capsaicin-sensitive afferents in guinea-pig bronchi through a ruthenium red-sensitive pathway. Br J Pharmacol. 1991 Sep;104(1):49–52. doi: 10.1111/j.1476-5381.1991.tb12383.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mizumura K., Sato J., Kumazawa T. Comparison of the effects of prostaglandins E2 and I2 on testicular nociceptor activities studied in vitro. Naunyn Schmiedebergs Arch Pharmacol. 1991 Sep;344(3):368–376. doi: 10.1007/BF00183013. [DOI] [PubMed] [Google Scholar]
  33. Moncada S., Ferreira S. H., Vane J. R. Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirin-like drugs in the dog knee joint. Eur J Pharmacol. 1975 Apr;31(2):250–260. doi: 10.1016/0014-2999(75)90047-3. [DOI] [PubMed] [Google Scholar]
  34. Naruse K., McGehee D. S., Oxford G. S. Differential responses of Ca-activated K channels to bradykinin in sensory neurons and F-11 cells. Am J Physiol. 1992 Feb;262(2 Pt 1):C453–C460. doi: 10.1152/ajpcell.1992.262.2.C453. [DOI] [PubMed] [Google Scholar]
  35. Otsuka M., Konishi S. Release of substance P-like immunoreactivity from isolated spinal cord of newborn rat. Nature. 1976 Nov 4;264(5581):83–84. doi: 10.1038/264083a0. [DOI] [PubMed] [Google Scholar]
  36. Perry D. C., Snyder S. H. Identification of bradykinin in mammalian brain. J Neurochem. 1984 Oct;43(4):1072–1080. doi: 10.1111/j.1471-4159.1984.tb12846.x. [DOI] [PubMed] [Google Scholar]
  37. Privitera P. J., Daum P. R., Hill D. R., Hiley C. R. Autoradiographic visualization and characteristics of [125I]bradykinin binding sites in guinea pig brain. Brain Res. 1992 Apr 10;577(1):73–79. doi: 10.1016/0006-8993(92)90539-l. [DOI] [PubMed] [Google Scholar]
  38. Proud D., Kaplan A. P. Kinin formation: mechanisms and role in inflammatory disorders. Annu Rev Immunol. 1988;6:49–83. doi: 10.1146/annurev.iy.06.040188.000405. [DOI] [PubMed] [Google Scholar]
  39. Regoli D., Barabé J. Pharmacology of bradykinin and related kinins. Pharmacol Rev. 1980 Mar;32(1):1–46. [PubMed] [Google Scholar]
  40. Sametz W., Juan H. Release of different prostaglandins from vascular tissue by different stimulators. Prostaglandins Leukot Med. 1982 Dec;9(6):593–602. doi: 10.1016/0262-1746(82)90017-8. [DOI] [PubMed] [Google Scholar]
  41. Santicioli P., Del Bianco E., Tramontana M., Geppetti P., Maggi C. A. Release of calcitonin gene-related peptide like-immunoreactivity induced by electrical field stimulation from rat spinal afferents is mediated by conotoxin-sensitive calcium channels. Neurosci Lett. 1992 Mar 2;136(2):161–164. doi: 10.1016/0304-3940(92)90039-a. [DOI] [PubMed] [Google Scholar]
  42. Saria A., Martling C. R., Yan Z., Theodorsson-Norheim E., Gamse R., Lundberg J. M. Release of multiple tachykinins from capsaicin-sensitive sensory nerves in the lung by bradykinin, histamine, dimethylphenyl piperazinium, and vagal nerve stimulation. Am Rev Respir Dis. 1988 Jun;137(6):1330–1335. doi: 10.1164/ajrccm/137.6.1330. [DOI] [PubMed] [Google Scholar]
  43. Steranka L. R., Manning D. C., DeHaas C. J., Ferkany J. W., Borosky S. A., Connor J. R., Vavrek R. J., Stewart J. M., Snyder S. H. Bradykinin as a pain mediator: receptors are localized to sensory neurons, and antagonists have analgesic actions. Proc Natl Acad Sci U S A. 1988 May;85(9):3245–3249. doi: 10.1073/pnas.85.9.3245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Taiwo Y. O., Bjerknes L. K., Goetzl E. J., Levine J. D. Mediation of primary afferent peripheral hyperalgesia by the cAMP second messenger system. Neuroscience. 1989;32(3):577–580. doi: 10.1016/0306-4522(89)90280-7. [DOI] [PubMed] [Google Scholar]
  45. Taiwo Y. O., Levine J. D. Further confirmation of the role of adenyl cyclase and of cAMP-dependent protein kinase in primary afferent hyperalgesia. Neuroscience. 1991;44(1):131–135. doi: 10.1016/0306-4522(91)90255-m. [DOI] [PubMed] [Google Scholar]
  46. Taiwo Y. O., Levine J. D. Prostaglandins inhibit endogenous pain control mechanisms by blocking transmission at spinal noradrenergic synapses. J Neurosci. 1988 Apr;8(4):1346–1349. doi: 10.1523/JNEUROSCI.08-04-01346.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Thayer S. A., Perney T. M., Miller R. J. Regulation of calcium homeostasis in sensory neurons by bradykinin. J Neurosci. 1988 Nov;8(11):4089–4097. doi: 10.1523/JNEUROSCI.08-11-04089.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Weinreich D. Bradykinin inhibits a slow spike afterhyperpolarization in visceral sensory neurons. Eur J Pharmacol. 1986 Dec 2;132(1):61–63. doi: 10.1016/0014-2999(86)90010-5. [DOI] [PubMed] [Google Scholar]
  49. Weinreich D., Wonderlin W. F. Inhibition of calcium-dependent spike after-hyperpolarization increases excitability of rabbit visceral sensory neurones. J Physiol. 1987 Dec;394:415–427. doi: 10.1113/jphysiol.1987.sp016878. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES