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Binding characteristics of delta opioid receptors in different regions of the brain of young and old male rats as studied with the highly selective ligand [D-PEN2-D-PEN5] enkephalin

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Abstract

The present experiments were performed to study the binding characteristics of delta opioid receptors in membrane preparations obtained from the brain of adult male rats, and to analyze whether aging modifies these binding parameters.

The binding characteristics of delta opioid receptors were evaluated on membrane preparations derived from dissected brain regions (hypothalamus, amygdala, mesencephalon, corpus striatum, hippocampus, thalamus, frontal poles, anterior and posterior cortex) collected from male rats of 3 and 24 months of age; the highly selective ligand 3H-[D-Pen2-D-Pen5] enkephalin (3H-DPDPE) was used.

The results obtained in young rats show that the distribution of delta opioid receptors is different in the various brain areas examined; these receptors appear to be maximally concentrated in the frontal poles, anterior and posterior cortex; lower concentrations were found in the other structures considered. Kd (dissociation constant) for the delta sites was found very similar in all areas. The distribution of delta opioid receptors in the brain of 24-month-old rats was similar to that observed in young animals; this result was surprising in view of the fact that aging modifies the number of other types of brain opioid receptors (mu and kappa). (Aging Clin. Exp. Res. 4: 69–75,1992)

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References

  1. Paterson S.J., Robertson L.E., Kosterlitz H.V.: Classification of opioid receptors. Br. Med. Bull. 39: 31–36, 1983.

    PubMed  CAS  Google Scholar 

  2. Quirion R., Zaiac J.M., Morgat J.L., Roques B.P.: Autoradiographic distribution of mu and delta receptors in rat brain using highly selective ligands. Life Sci. 33: 227–230, 1983.

    Article  PubMed  CAS  Google Scholar 

  3. Gulya K., Gehlert D.R., Wamsley J.K., Mosberg H., Hruby V.J., Yamamura H.I.: Light microscopic autoradiographic localization of delta opioid receptors in the rat brain using a highly selective Bis-Penicillamine cyclic enkephalin analog. J. Pharmacol. Exp. Ther. 238: 720–726, 1986.

    PubMed  CAS  Google Scholar 

  4. Mansour A., Lewis M.E., Khachaturian H., Akil H., Watson S.J.: Pharmacological and anatomical evidence of selective μ, δ, and k opioid receptor binding in rat brain. Brain Res. 399: 69–79, 1986.

    Article  PubMed  CAS  Google Scholar 

  5. McLean S., Rothman R.B., Herkenham M.: Autoradiographic localization of μ- and δ-opiate receptors in the forebrain of the rat. Brain Res. 378: 49–60, 1986.

    Article  PubMed  CAS  Google Scholar 

  6. Mansour A., Khachaturian H., Lewis M.E., Akil H., Watson S.J.: Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain. J. Neurosci. 7: 2445–2464, 1987.

    PubMed  CAS  Google Scholar 

  7. Tempel A., Zukin R.S.: Neuroanatomical patterns of the μ, δ and k opioid receptors of rat brain as determined by quantitative in vitro autoradiography. Proc. Natl. Acad. Sci. USA 84: 4308–4312, 1987.

    Article  PubMed  CAS  Google Scholar 

  8. Mansour A., Khachaturian H., Lewis M.E., Akil H., Watson S.J.: Anatomy of CNS opioid receptors. Trends in Neurosci. 11: 308–314,1988.

    Article  CAS  Google Scholar 

  9. Sharif N.A., Hughes J.: Discrete mapping of brain mu and delta opioid receptors using selective peptides: quantitative autoradiography, species differences and comparison with kappa receptors. Peptides 10: 499- 522, 1989.

    Article  PubMed  CAS  Google Scholar 

  10. Akiyama K., Gee K.W., Mosberg H.I., Hruby V.J., Yamamura H.I.: Characterization of [3H][2-D-penicillamine, 5-D-penicillamine]-enkephalin binding to δ opiate receptors in the rat brain and neuroblastomaglioma hybrid cell line (NG 108-15). Proc. Natl. Acad. Set. USA 82: 2543–2547, 1985.

    Article  CAS  Google Scholar 

  11. Castanas E., Blanc D., Bourhim N., Cupo A., Cantau P., Giraud P.: Reassessment of opioid binding sites in the rat brain. Neuropeptides 7: 369–380, 1986.

    Article  PubMed  CAS  Google Scholar 

  12. Chang K.J., Cooper B.R., Hazum E., Cuatrecasas P.: Multiple opiate receptors: different regional distribution in the brain and differential binding of opiates and opioid peptides. Mol. Pharmacol. 16: 91–104, 1979.

    PubMed  CAS  Google Scholar 

  13. Robson L.E.,Gillan M.G.C., Kosterlitz H.W.: Species differences in the concentrations and distributions of opioid binding sites. Eur. J. Pharmacol. 112: 65–71, 1985.

    Article  PubMed  CAS  Google Scholar 

  14. Corbett A.D:, Gillan M.G.C., Kosterlitz H.W., McKnight A.T., Paterson S.J., Robson L.E.: Selectivities of opioid peptide analogues as agonists and antagonists at the δ-receptor. Br. J. Pharmacol. 83: 271–279, 1984.

    Article  PubMed  CAS  Google Scholar 

  15. Cotton R., Kosterlitz H.W., Paterson S.J., Ranee M.J., Traynor J.R.: The use of 3[H]-[D-Pen2,D- Pen5]enkephalin as a highly selective ligand for the δ- binding site. Br. J. Pharmacol. 84: 927–932, 1985.

    Article  PubMed  CAS  Google Scholar 

  16. Mosberg H.I., Hurst R., Hruby V.J., Gee K., Yamamura H.I., Galligan J.J., Burks T.F.: Bis-penicillamine enkephalins possess highly improved specificity toward δ opioid receptors. Proc. Natl. Acad. Sci. USA 80: 5871–5874, 1983.

    Article  PubMed  CAS  Google Scholar 

  17. Barden N., Dupont A., Labrie F., Merand Y., Roleau D., Vaudry H., Boissier J.R.: Age-dependent changes in the β-endorphin content of discrete rat brain nuclei. Brain Res. 208: 209–212, 1981.

    Article  PubMed  CAS  Google Scholar 

  18. Dupont A., Savard P., Merand Y., Labrie F., Boissier J.R.: Age-related changes in central nervous system enkephalins and substance P. Life Sci. 29: 2317–2322, 1981.

    Article  PubMed  CAS  Google Scholar 

  19. Forman L.J., Sonntag W.E., Van Vugt D.A., Meites J.: Immunoreactive β-endorphin in the plasma, pituitary and hypothalamus of young and old male rats. Neurobiol. Aging 2: 281–284, 1981.

    Article  PubMed  CAS  Google Scholar 

  20. Gambert S.R.: Interaction of age and thyroid hormone status on beta-endorphin content in rat corpus striatum and hypothalamus. Neuroendocrinology 32: 114- 117, 1981.

    Article  PubMed  CAS  Google Scholar 

  21. Gambert S.R., Garthwaite T.L., Pontrer C.H., Hägen T.C.: Age-related changes in central nervous system of beta-endorphin and ACTH. Neuroendocrinology 31: 252–255, 1980.

    Article  PubMed  CAS  Google Scholar 

  22. Steger R.W., Sonntag W.E., Van Vugt D.A., Forman L.J., Meites J.: Reduced ability of naloxone to stimulate LH and testosterone release in aging male rats: possible relation to increase in hypothalamic metenkephalin. Life Sci. 27: 747–753, 1980.

    Article  PubMed  CAS  Google Scholar 

  23. Tang F., Tang J., Chau J., Costa E.: Age-related and diurnal changes in Met5-Enk-Arg6-Phe7 and Met5- enkephalin contents of pituitary and rat brain structures. Life Sci. 35: 1005–1014, 1984.

    Article  PubMed  CAS  Google Scholar 

  24. Hess G.D., Joseph J.A., Roth G.S:: Effect of age on sensitivity to pain and brain opiate receptors. Neurobiol. Aging 2: 49–55, 1981.

    Article  PubMed  CAS  Google Scholar 

  25. Neisewander J.L., Nonneman A.J., McDougall S.A., Bardo M.T.: Up-regulation of opiate receptors following chronic naloxone treatment in aged rats. Neurobiol. Aging 10: 55–58, 1989.

    Article  PubMed  CAS  Google Scholar 

  26. Maggi R., Limonta P., Dondi D., Martini L., Piva F.: Distribution of kappa opioid receptors in the brain of young and old male rats. Life Sci. 45: 2085–2092, 1989.

    Article  PubMed  CAS  Google Scholar 

  27. Messing R.B., Vasquez B.J., Samaniego B., Jensen R.A., Martinez J.L., McGaugh J.L.: Alterations in dihydromorphine binding in cerebral hemispheres of aged male rats. J. Neurochem. 36: 784–790, 1981.

    Article  PubMed  CAS  Google Scholar 

  28. Petkov V.V., Petkov V.D., Grahovska T., Konstantinova E.: Enkephalin receptor changes in rat brain during aging. Gen. Pharmacol. 15: 491–495, 1984.

    Article  PubMed  CAS  Google Scholar 

  29. Piva F., Maggi R., Limonta P., Dondi D., Martini L: Decrease of mu opioid receptors in the brain and in the hypothalamus of the aged male rat. Life Sci. 40: 391–398, 1987.

    Article  PubMed  CAS  Google Scholar 

  30. Munson P.J., Rodbard D.: Computerized analysis of ligand binding data: basic principles and recent developments. In: Rodbard D., Forti G. (Eds.), Computers in Endocrinology. Raven Press, New York, 1984, vol. 14, pp. 117–145.

    Google Scholar 

  31. Bradford M.M.: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248–254, 1976.

    Article  PubMed  CAS  Google Scholar 

  32. Olasmaa M., Limonta P., Maggi R., Dondi D., Martini L., Piva F.: Further evidence that gonadal steroids do not modulate brain opiate receptors in male rats. Endocrinol. Jpn. 34: 521–529, 1987.

    Article  PubMed  CAS  Google Scholar 

  33. Munson P.J., Rodbard D.: LIGAND: a versatile computerized approach for characterization of ligand-binding systems. Anal. Biochem. 107: 220–239, 1980.

    Article  PubMed  CAS  Google Scholar 

  34. Feldman H.A.: Mathematical theory of complex ligand-binding systems at equilibrium: some methods for parameter fitting. Anal. Biochem. 48: 317–338,1972.

    Article  PubMed  CAS  Google Scholar 

  35. Ueno E., Duan Liu D., Ho I.K., Hoskins B.: Opiate receptor characteristics in brain from young, mature and aged mice. Neurobiol. Aging 9: 279–283, 1988.

    Article  PubMed  CAS  Google Scholar 

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Dondi, D., Maggi, R., Limonta, P. et al. Binding characteristics of delta opioid receptors in different regions of the brain of young and old male rats as studied with the highly selective ligand [D-PEN2-D-PEN5] enkephalin. Aging Clin Exp Res 4, 69–75 (1992). https://doi.org/10.1007/BF03324070

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