Advertisement

Acta Biologica Hungarica

, Volume 57, Issue 3, pp 283–294 | Cite as

Restoration of Morphine-Induced Alterations in Rat Submandibular Gland Function by N-Methyl-D-Aspartate Agonist

  • N. Hashemi
  • Azadeh Mohammadirad
  • Zahra Bayrami
  • R. Khorasani
  • Sanaz Vosough
  • Atousa Aliahmadi
  • Shekoufeh Nikfar
  • M. Sharifzadeh
  • A. Kebriaeezadeh
  • M. AbdollahiEmail author
Article

Abstract

The effects of morphine, 1-aminocyclobutane-cis-1,3-dicarboxylic (ACBD; NMDA agonist) and 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphoric acid (CPP; NMDA antagonist) and their concurrent therapy on rat submandibular secretory function were studied. Pure submandibular saliva was collected intra-orally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Intraperitoneal injection of morphine (6 mg/kg) induced significant inhibition of salivary flow rate, total protein, calcium, and TGF-β1 concentrations. Administration of ACBD (10 mg/kg) and CPP (10 mg/kg) alone did not influence secretion of submandibular glands. In combination therapy, coadministration of CPP with morphine did not influence morphine-induced changes in salivary function while ABCD could restore all morphine-induced changes. In combination treatment, ACBD prevented morphine-induced reduction of flow rate, total protein, calcium, and TGF-β1 and reached control levels. It is concluded that morphine-induced alterations in submandibular gland function are mediated through NMDA receptors.

Keywords

1-aminocyclobutane-cis-1,3-dicarboxylic 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphoric acid N-methyl-D-aspartate morphine submandibular gland saliva 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgments

This work was supported by a grant from National Excellency of Toxicology and Food Chemistry, TUMS.

References

  1. 1.
    Abdollahi, M., Radfar, M. (2003) A review of drug-induced oral reactions. J. Contemp. Dent. Pract. 4, 10–31.CrossRefGoogle Scholar
  2. 2.
    Abdollahi, M., Safarhamidi, H. (2002) Protection by nitric oxide of morphine-induced inhibition of rat submandibular gland function. Pharmacol. Res. 45, 87–92.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Abdollahi, M., Simaiee, B. (2003) Stimulation by theophylline and sildenafil of rat submandibular secretion of protein, epidermal growth factor and flow rate. Pharmacol. Res. 48, 445–449.CrossRefGoogle Scholar
  4. 4.
    Abdollahi, M., Sarrafzadeh, J., Nikfar, S., Roshanzamir, F. (2003) Mechanism of aspartame-induced antinociception in mice. Indian J. Pharmacol. 35, 37–41.Google Scholar
  5. 5.
    Abdollahi, M., Dehpour, A. R., Baharnouri, G. (1998) Effects of rubidium on the secretory function of the rat submandibular gland. Toxic. Subs. Mech. 17, 121–131.CrossRefGoogle Scholar
  6. 6.
    Abdollahi, M., Dehpour, A. R., (2000) Kazemian P. Alteration by cadmium of rat submandibular gland secretory function and the role of the L-arginine/nitric oxide pathway. Pharmacol. Res. 42.Google Scholar
  7. 7.
    Abdollahi, M., Dehpour, A. R., Fooladgar, M. (1997) Alteration of rat submandibulary gland secretion of protein, calcium and N-acetyl-beta-D-glucosaminidase activity by lead. Gen. Pharmacol. 29, 675–680.CrossRefGoogle Scholar
  8. 8.
    Abdollahi, M., Sharifzadeh, M., Marzban, H., Abri, G. H., Torab-Jahromi, M. (1999) Alteration by lead acetate of rats submandibular gland morphology and ultrastructure. Toxic. Subs. Mech. 18, 139–148.CrossRefGoogle Scholar
  9. 9.
    Abdollahi, M., Dehpour, A. R., Shafayee, F. (2000) L-arginine/nitric oxide pathway and interaction with lead acetate on rat submandibulary gland function. Pharmacol. Toxicol. 87, 198–203.CrossRefGoogle Scholar
  10. 10.
    Aub, D. L., Putney, J. W., (1987) Mobilization of intracellular calcium by methacholine and inositol 1,4,5-triphosphate in rat parotid acinar cells. J. Dent. Res. 66, 547–551.CrossRefGoogle Scholar
  11. 11.
    Avidor-Reiss, T., Nevo, I., Levy, R., Pfeuffer, T., Vogel, Z. (1996) Chronic opioid treatment induces adenylyl cyclase V superactivation. Involvement of Gbetagamma. J. Biol. Chem. 271, 21309–21315.CrossRefGoogle Scholar
  12. 12.
    Avidor-Reiss, T., Bayewitch, M., Levy, R., Matus-Leibovitch, N., Nevo, I., Vogel, Z. (1995) Adenylylcyclase supersensitization in mu-opioid receptor-transfected Chinese hamster ovary cells following chronic opioid treatment. J. Biol. Chem. 270, 29732–29738.CrossRefGoogle Scholar
  13. 13.
    Baum, B. J. (1987) Neurotransmitter control of secretion. J. Dent. Res. 66, 628–632.CrossRefGoogle Scholar
  14. 14.
    Ben-Eliyahu, S., Marek, P., Vaccarino, A. L., Mogil, J. S., Sternberg, W. F., Liebeskind, J. C., (1992) The NMDA receptor antagonist MK-801 prevents long-lasting non-associative morphine tolerance in the rat. Brain Res. 575, 304–308.CrossRefGoogle Scholar
  15. 15.
    Bhat, R. S., Bhaskaran, M., Mongia, A., Hitosugi, N., Singhal, P. C., (2004) Morphine-induced macrophage apoptosis: oxidative stress and strategies for modulation. J. Leukoc. Biol. 75, 1131–1138.CrossRefGoogle Scholar
  16. 16.
    Blake, A. D., Bot, G., Freeman, J. C., Reisine, T. (1997) Differential opioid agonist regulation of the mouse mu opioid receptor. J. Biol. Chem. 272, 782–790.CrossRefGoogle Scholar
  17. 17.
    Castle, J. D., Arvan, P., Cameron, R. (1987) Protein production and secretion in exocrine cell. J. Dent. Res. 66, 633–637.CrossRefGoogle Scholar
  18. 18.
    Celerier, E., Laulin, J. P., Larcher, A., Moal, M. L., Simonnet, G. (1999) Evidence for opiate-activated NMDA processes masking opiate analgesia rats. Brain Res. 18–25.Google Scholar
  19. 19.
    Chao, C. C., Hu, S., Molitor, T. W., Zhou, Y., Murtaugh, M. P., Tsang, M., Peterson, P. K., (1992) Morphine potentiates transforming growth factor-beta release from human peripheral blood mononuclear cell cultures. J. Pharmacol. Exp. Ther. 262, 19–24.PubMedGoogle Scholar
  20. 20.
    Chen, L., Huang, L. Y., (1991) Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C by a mu opioid. Neuron. 7, 319–326.CrossRefGoogle Scholar
  21. 21.
    Drolet, G., Dumont, E. C., Gosselin, I., Kinkead, R., Laforest, S., Trottier, J. F., (2001) Role of endogenous opioid system in the regulation of the stress response. Prog. Neuropsychopharmacol. Biol. Psychiatry 25, 729–741.CrossRefGoogle Scholar
  22. 22.
    Edgar, W. M. (1992) Saliva: its secretion, composition and functions. Br. Dent. J. 172, 305–312.CrossRefGoogle Scholar
  23. 23.
    Endoh, T., Suzuki, T. (1998) The regulation manner of opioid receptors on distinct types of calcium channels in hamster submandibular ganglion cells. Arch. Oral. Biol. 43, 221–233.CrossRefGoogle Scholar
  24. 24.
    Edwards, A. V., Garrett, J. R., (1993) Nitric oxide-related vasodilator responses to parasympathetic stimulation of the submandibular gland in the cat. J. Physiol. 464, 379–392.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Fernandez, F. J., Khan, H. L., (1971) Clinical methods for atomic absorption spectroscopy. Clin. Chem. Newslett. 24, 190–195.Google Scholar
  26. 26.
    Fields, A., Sarne, Y. (1997) The stimulatory effect of opioids on cyclic AMP production in SK-N-SH cells is mediated by calcium ions. Life Sci. 61, 595–602.CrossRefGoogle Scholar
  27. 27.
    Fundytus, M. E., Coderre, T. J., (1996) Chronic inhibition of intracellular Ca2+ release or protein kinase C activation significantly reduces the development of morphine dependence. Eur. J. Pharmacol. 300, 173–181.CrossRefGoogle Scholar
  28. 28.
    Garthwaite, J. (1991) Glutamate, nitric oxide and cell-cell signaling in the nervous system. Trends Neurosci. 14, 60–67.CrossRefGoogle Scholar
  29. 29.
    Hanania, T., Johnson, K. M., (1998) Regulation of neurotransmitter release by endogenous nitric oxide in striatal slices. Eur. J. Pharmacol. 359, 111–117.CrossRefGoogle Scholar
  30. 30.
    Helmeste, D. M., Tang, S. W., (1998) The role of calcium in the etiology of the affective disorders. Jpn. J. Pharmacol. 77, 107–116.CrossRefGoogle Scholar
  31. 31.
    Hirst, R. A., Lambert, D. G., (1995) Adenylyl cyclase in SH-SY5Y human neuroblastoma cells is regulated by intra-and extracellular calcium. Biochem. Pharmacol. 49, 1633–1640.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Jin, W., Terman, G. W., Chavkin, C. (1997) Kappa opioid receptor tolerance in the guinea pig hippocampus. J. Pharmacol. Exp. Ther. 281, 123–128.PubMedGoogle Scholar
  33. 33.
    Johnson, P. S., Wang, J. B., Wang, W. F., Uhl, G. R., (1994) Expressed mu opiate receptor couples to adenylate cyclase and phosphatidyl inositol turnover. Neuroreport 5, 507–509.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kitamura, Y., Miyazaki, A., Yamanaka, Y., Nomura, Y. (1993) Stimulatory effects of protein kinase C and calmodulin kinase II on N-methyl-D-aspartate receptor/channels in the postsynaptic density of rat brain. J. Neurochem. 61, 100–109.CrossRefGoogle Scholar
  35. 35.
    Kobayashi, M., Nemoto, T., Nagata, H., Konno, A., Chiba, T. (1997) Immunohistochemical studies on glutamatergic, GABAergic and glycinergic axon varicosities presynaptic to parasympathetic preganglionic neurons in the superioi salivatory nucleus of the rat. Brain Res. 766, 72–82.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Kojima, H., Nakatsubo, N., Kikuchi, K., Urano, Y., Higuchi, T., Tanaka, J., Kudo, Y., Nagano, T. (1998) Direct evidence of NO production in rat hippocampus and cortex using a new fluorescent indicator: DAF-2 DA. Neuroreport 9, 3345–3348.CrossRefGoogle Scholar
  37. 37.
    Lin, L. H., Agassandian, K., Fujiyama, F., Kaneko, T., Talmas, W. T., (2003) Evidence for a glutamatergic input to pontin preganglionic neurons of the superior salivary nucleus in rat. J. Chem. Neuroanat. 25, 261–268.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Liu, J. G., Anand, K. J., (2001) Protein kinases modulate the cellular adaptations associated with opioidtolerance and dependence. Brain Res. Brain Res. Rev. 38, 1–19.CrossRefGoogle Scholar
  39. 39.
    Lohinai, Z., Szekeli, A. D., Soos, L., Feher, E. (1995) Distribution of nitric oxide synthase containing elements in the feline submandibular gland. Neurosci. Lett. 192, 9–12.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Lowry, O. H., Roserbrough, N. J., Farr, A. L., Randell, R. J., (1951) Protein measurement with the folin phenol reagent. J. Biol. Chem. 193, 265–275.Google Scholar
  41. 41.
    Martin, G., Nie, Z., Siggins, G. R., (1997) mu-Opioid receptors modulate NMDA receptor-mediated responses in nucleus accumbens neurons. J. Neurosci. 17, 11–22.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Mayer, D. J., Mao, J., Price, D. D., (1995) The development of morphine tolerance and dependence is associated with translocation of protein kinase. C. Pain. 61, 365–374.CrossRefGoogle Scholar
  43. 43.
    Menendez, L., Hidalgo, A., Baamonde, A. (1997) Spinal calmodulin inhibitors reduce N-methyl-D-aspartate- and septide-induced nociceptive behavior. Eur. J. Pharmacol. 335, 9–14.CrossRefGoogle Scholar
  44. 44.
    Nestler, E. J., Aghajanian, G. K., (1997) Molecular and cellular basis of addiction. Science 278, 58–63.CrossRefGoogle Scholar
  45. 45.
    Podhorna, J., Brown, R. E., (2000) Interaction between N-methyl-D-aspartate and nitric oxide in the modulation of ultrasonic vocalizations of infant rats. Eur. J. Pharmacol. 408, 265–271.CrossRefGoogle Scholar
  46. 46.
    Rezaie, S., Rezaie, A., Minaiee, B., Khorasani, R., Abdollahi, M. (2005) On the relation of nitric oxide to nifedipine-induced gingival hyperplasia and impaired submandibular glands function in rats in vivo. Fund. Clin. Pharmacol. 19, 65–71.CrossRefGoogle Scholar
  47. 47.
    Ahmed, A. O., Sharifzadeh, M., Nikfar, S., Jamshidi, H. R., Abdollahi, M. (2006) Prevention by L-arginine/nitric oxide of chlordiazepoxide-induced toxic reactions in the rat salivary gland. Toxicol. Mech. Methods 16, 331–337.CrossRefGoogle Scholar
  48. 48.
    Sanchez-Blazquez, P., Rodriguez-Diaz, M., Frejo, M. T., Garzon, J. (1999) Stimulation of mu- and delta-opioid receptors enhances phosphoinositide metabolism in mouse spinal cord: evidence for subtypes of delta-receptors. Eur. J. Neurosci. 11, 2059–2064.CrossRefGoogle Scholar
  49. 49.
    Sanger, D. J., Joly, D. (1991) The effects of NMDA antagonists on punished exploration in mice. Behav. Pharmacol. 2, 57–63.PubMedGoogle Scholar
  50. 50.
    Schachter, M., Matthews, B., Bhoola, K. D., (1992) Evidence that nitric oxide or a related substance is a neurovasodilator in the submandibular gland of cat. Agents. Actions 38, 366–370.PubMedGoogle Scholar
  51. 51.
    Shida, T., Kondo, E., Ueda, Y., Takai, N., Yoshida, Y., Araki, T., Kiyama, H., Tohyama, M. (1995) Role of amino acids in salivation and the localization of their receptors in the rat salivary gland. Brain. Res. Mol. Brain. Res. 33, 261–268.CrossRefGoogle Scholar
  52. 52.
    Shoaib, M., Schindler, C. W., Goldberg, S. R., Pauly, J. R., (1997) Behavioural and biochemical adaptations to nicotine in rats: influence of MK801, an NMDA receptor antagonist. Psychopharmacology (Berl.) 134, 121–130.CrossRefGoogle Scholar
  53. 53.
    Smart, D., Lambert, D. G., (1996) delta-Opioids stimulate inositol 1,4,5-trisphosphate formation, and so mobilize Ca2+ from intracellular stores, in undifferentiated NG108-15 cells. J. Neurochem. 66, 1462–1467.CrossRefGoogle Scholar
  54. 54.
    Smith, F. L., Lohmann, A. B., Dewey, W. L., (1999) Involvement of phospholipid signal transduction pathways in morphine tolerance in mice. Br. J. Pharmacol. 128, 220–226.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Sreebny, L. M. (2000) Saliva in health and disease: an appraisal and update. Int. Dent. J. 50, 140–161.CrossRefGoogle Scholar
  56. 56.
    Suddick, R. P., Shannon, I. L., (1970) Salivary Na+, K+, and Cl-secretion rates relationship to a fluid generation mechanism. Jpn. J. Physiol. 20, 540–549.CrossRefGoogle Scholar
  57. 57.
    Vivien, D., Ali, C. (2005) Transforming growth factor-beta signaling in brain disorder. Cytokine Growth Factor Rev. 2005 [Epud ahead of print]Google Scholar
  58. 58.
    Wang, Z., Bilsky, E. J., Porreca, F., Sadee, W. (1994) Constitutive ώ opioid receptor activation as a regulatory mechanism underlying narcotic tlerance and dependence. Life Sci. 54.Google Scholar
  59. 59.
    White, I. D., Hoskin, P. J., Hanks, G. W., Bliss, J. M., (1989) Morphine and dryness of the mouth. B. M. J. 298, 1222–1223.CrossRefGoogle Scholar
  60. 60.
    Xu, Z., Wu, J., Wang, B., Wang, W. (1998) Distribution of morphine in acute morphine-treated rats. Hua Xi Yi Ke Da Xue Xue Bao 29, 29–32.PubMedGoogle Scholar
  61. 61.
    Yoshida, Y., Sprecher, R. L., Schneyer, C. A., Schneyer, L. H., (1967) Role of α-receptors in sympathetic regulation of electrolytes in rat submaxillary saliva. Proc. Soc. Exp. Biol. Med. 126, 912–916.CrossRefGoogle Scholar
  62. 62.
    Zhang, J., Synder, S. H., (1995) Nitric oxide in the nervous system. Annu. Rev. Pharmacol. Toxicol. 35, 213–233.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest 2006

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • N. Hashemi
    • 1
  • Azadeh Mohammadirad
    • 1
  • Zahra Bayrami
    • 1
  • R. Khorasani
    • 1
  • Sanaz Vosough
    • 1
  • Atousa Aliahmadi
    • 1
  • Shekoufeh Nikfar
    • 1
  • M. Sharifzadeh
    • 1
  • A. Kebriaeezadeh
    • 1
  • M. Abdollahi
    • 1
    Email author
  1. 1.Department of Pharmacology and Toxicology, Faculty of Pharmacy, and Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran

Personalised recommendations