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. 1996 Jun 1;316(Pt 2):539–544. doi: 10.1042/bj3160539

Cyclic GMP regulates activation of phosphoinositidase C by bradykinin in sensory neurons.

J S Harvey 1, G M Burgess 1
PMCID: PMC1217382  PMID: 8687398

Abstract

Prior exposure of cultured neonatal rat dorsal root ganglion (DRG) neurons to bradykinin resulted in marked attenuation of bradykinin-induced activation of phosphoinositidase C (PIC). The (logconcentration)-response curve for bradykinin-induced [3H]inositol trisphosphate ([3H]IP3) formation was shifted to the right and the maximum response was reduced. Bradykinin increases cyclic GMP (cGMP) in DRG neurons [Burgess, Mullaney, McNeill, Coote, Minhas and Wood (1989) J. Neurochem. 53, 1212-1218] and treatment of the neurons with dibutyryl cGMP (dbcGMP) had a similar, inhibitory, effect on bradykinin-induced [3H]IP3 formation. NG-Nitro-L-arginine (LNNA) blocked bradykinin-induced formation of cGMP. It prevented the functional uncoupling induced by pretreatment with bradykinin, but not the inhibitory effect of dbcGMP on [3H]IP3 formation. The ability of LNNA to prevent desensitization was reversed by excess L-arginine, indicating that its actions were mediated through inhibition of nitric oxide synthase. In addition to functional desensitization, exposure to bradykinin reduced the number of cell-surface receptors detected with [3H]bradykinin, without affecting its KD value for the remaining sites. In contrast to bradykinin, pretreatment with dbcGMP had no effect on either the KD or B(max) for [3H]bradykinin binding. This implies that the inhibitory effect of dbcGMP was down-stream from the binding of bradykinin to its receptor and upstream of IP3 formation. The lack of effect of dbcGMP on [3H]bradykinin binding suggests that the decrease in receptor number induced by bradykinin was mediated by a different mechanism and was not a key factor in the rapid phase of desensitization in these cells.

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Selected References

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  1. Bauer M. B., Simmons M. L., Murphy S., Gebhart G. F. Bradykinin and capsaicin stimulate cyclic GMP production in cultured rat dorsal root ganglion neurons via a nitrosyl intermediate. J Neurosci Res. 1993 Oct 15;36(3):280–289. doi: 10.1002/jnr.490360306. [DOI] [PubMed] [Google Scholar]
  2. Bouvier M., Leeb-Lundberg L. M., Benovic J. L., Caron M. G., Lefkowitz R. J. Regulation of adrenergic receptor function by phosphorylation. II. Effects of agonist occupancy on phosphorylation of alpha 1- and beta 2-adrenergic receptors by protein kinase C and the cyclic AMP-dependent protein kinase. J Biol Chem. 1987 Mar 5;262(7):3106–3113. [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Dray A., Patel I. A., Perkins M. N., Rueff A. Bradykinin-induced activation of nociceptors: receptor and mechanistic studies on the neonatal rat spinal cord-tail preparation in vitro. Br J Pharmacol. 1992 Dec;107(4):1129–1134. doi: 10.1111/j.1476-5381.1992.tb13418.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eggerickx D., Raspe E., Bertrand D., Vassart G., Parmentier M. Molecular cloning, functional expression and pharmacological characterization of a human bradykinin B2 receptor gene. Biochem Biophys Res Commun. 1992 Sep 30;187(3):1306–1313. doi: 10.1016/0006-291x(92)90445-q. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Hess J. F., Borkowski J. A., Macneil T., Stonesifer G. Y., Fraher J., Strader C. D., Ransom R. W. Differential pharmacology of cloned human and mouse B2 bradykinin receptors. Mol Pharmacol. 1994 Jan;45(1):1–8. [PubMed] [Google Scholar]
  9. Hess J. F., Borkowski J. A., Young G. S., Strader C. D., Ransom R. W. Cloning and pharmacological characterization of a human bradykinin (BK-2) receptor. Biochem Biophys Res Commun. 1992 Apr 15;184(1):260–268. doi: 10.1016/0006-291x(92)91187-u. [DOI] [PubMed] [Google Scholar]
  10. Hösli E., Hösli L. Autoradiographic localization of binding sites for neuropeptide Y and bradykinin on astrocytes. Neuroreport. 1993 Feb;4(2):159–162. doi: 10.1097/00001756-199302000-00011. [DOI] [PubMed] [Google Scholar]
  11. Hösli L., Hösli E., Kaeser H., Lefkovits M. Colocalization of receptors for vasoactive peptides on astrocytes of cultured rat spinal cord and brain stem: electrophysiological effects of atrial and brain natriuretic peptide, neuropeptide Y and bradykinin. Neurosci Lett. 1992 Dec 14;148(1-2):114–116. doi: 10.1016/0304-3940(92)90817-q. [DOI] [PubMed] [Google Scholar]
  12. Johnston P. A., Jahn R., Südhof T. C. Transmembrane topography and evolutionary conservation of synaptophysin. J Biol Chem. 1989 Jan 15;264(2):1268–1273. [PubMed] [Google Scholar]
  13. Jong Y. J., Dalemar L. R., Wilhelm B., Baenziger N. L. Human bradykinin B2 receptors isolated by receptor-specific monoclonal antibodies are tyrosine phosphorylated. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10994–10998. doi: 10.1073/pnas.90.23.10994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klueppelberg U. G., Gates L. K., Gorelick F. S., Miller L. J. Agonist-regulated phosphorylation of the pancreatic cholecystokinin receptor. J Biol Chem. 1991 Feb 5;266(4):2403–2408. [PubMed] [Google Scholar]
  15. Luo H., Lindeman R. P., Chase H. S., Jr Participation of protein kinase C in desensitization to bradykinin and to carbachol in MDCK cells. Am J Physiol. 1992 Mar;262(3 Pt 2):F499–F506. doi: 10.1152/ajprenal.1992.262.3.F499. [DOI] [PubMed] [Google Scholar]
  16. McGehee D. S., Goy M. F., Oxford G. S. Involvement of the nitric oxide-cyclic GMP pathway in the desensitization of bradykinin responses of cultured rat sensory neurons. Neuron. 1992 Aug;9(2):315–324. doi: 10.1016/0896-6273(92)90170-i. [DOI] [PubMed] [Google Scholar]
  17. Munoz C. M., Cotecchia S., Leeb-Lundberg L. M. B2 kinin receptor-mediated internalization of bradykinin in DDT1 MF-2 smooth muscle cells is paralleled by sequestration of the occupied receptors. Arch Biochem Biophys. 1993 Mar;301(2):336–344. doi: 10.1006/abbi.1993.1153. [DOI] [PubMed] [Google Scholar]
  18. Munson P. J., Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980 Sep 1;107(1):220–239. doi: 10.1016/0003-2697(80)90515-1. [DOI] [PubMed] [Google Scholar]
  19. Olmos L., Mombouli J. V., Illiano S., Vanhoutte P. M. cGMP mediates the desensitization to bradykinin in isolated canine coronary arteries. Am J Physiol. 1995 Feb;268(2 Pt 2):H865–H870. doi: 10.1152/ajpheart.1995.268.2.H865. [DOI] [PubMed] [Google Scholar]
  20. Perney T. M., Miller R. J. Two different G-proteins mediate neuropeptide Y and bradykinin-stimulated phospholipid breakdown in cultured rat sensory neurons. J Biol Chem. 1989 May 5;264(13):7317–7327. [PubMed] [Google Scholar]
  21. Roscher A. A., Klier C., Dengler R., Faussner A., Müller-Esterl W. Regulation of bradykinin action at the receptor level. J Cardiovasc Pharmacol. 1990;15 (Suppl 6):S39–S43. [PubMed] [Google Scholar]
  22. Ruth P., Wang G. X., Boekhoff I., May B., Pfeifer A., Penner R., Korth M., Breer H., Hofmann F. Transfected cGMP-dependent protein kinase suppresses calcium transients by inhibition of inositol 1,4,5-trisphosphate production. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2623–2627. doi: 10.1073/pnas.90.7.2623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Takai Y., Kaibuchi K., Matsubara T., Nishizuka Y. Inhibitory action of guanosine 3', 5'-monophosphate on thrombin-induced phosphatidylinositol turnover and protein phosphorylation in human platelets. Biochem Biophys Res Commun. 1981 Jul 16;101(1):61–67. doi: 10.1016/s0006-291x(81)80010-1. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Tobin A. B., Nahorski S. R. Rapid agonist-mediated phosphorylation of m3-muscarinic receptors revealed by immunoprecipitation. J Biol Chem. 1993 May 5;268(13):9817–9823. [PubMed] [Google Scholar]
  26. Weintraub W. H., Negulescu P. A., Machen T. E. Calcium signaling in endothelia: cellular heterogeneity and receptor internalization. Am J Physiol. 1992 Nov;263(5 Pt 1):C1029–C1039. doi: 10.1152/ajpcell.1992.263.5.C1029. [DOI] [PubMed] [Google Scholar]
  27. Willars G. B., Nahorski S. R. Heterologous desensitization of both phosphoinositide and Ca2+ signaling in SH-SY5Y neuroblastoma cells: a role for intracellular Ca2+ store depletion? Mol Pharmacol. 1995 Mar;47(3):509–516. [PubMed] [Google Scholar]
  28. Wojcikiewicz R. J., Tobin A. B., Nahorski S. R. Desensitization of cell signalling mediated by phosphoinositidase C. Trends Pharmacol Sci. 1993 Jul;14(7):279–285. doi: 10.1016/0165-6147(93)90131-3. [DOI] [PubMed] [Google Scholar]
  29. Wolsing D. H., Rosenbaum J. S. Bradykinin-stimulated inositol phosphate production in NG108-15 cells is mediated by a small population of binding sites which rapidly desensitize. J Pharmacol Exp Ther. 1991 May;257(2):621–633. [PubMed] [Google Scholar]
  30. Wolsing D. H., Rosenbaum J. S. The mechanism for the rapid desensitization in bradykinin-stimulated inositol monophosphate production in NG108-15 cells involves interaction of a single receptor with multiple signaling pathways. J Pharmacol Exp Ther. 1993 Jul;266(1):253–261. [PubMed] [Google Scholar]

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