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. 1992 Jan 15;89(2):564–568. doi: 10.1073/pnas.89.2.564

Synaptic localization of kappa opioid receptors in guinea pig neostriatum.

C Jomary 1, J E Gairin 1, A Beaudet 1
PMCID: PMC48279  PMID: 1346233

Abstract

Distribution of kappa opioid receptors was examined by EM radioautography in sections of guinea pig neostriatum with the selective 125I-labeled dynorphin analog [D-Pro10]dynorphin-(1-11). Most specifically labeled binding sites were found by probability circle analysis to be associated with neuronal membrane appositions. Because of limitations in resolution of the method, the radioactive sources could not be ascribed directly to either one of the apposed plasma membranes. Nevertheless, three lines of evidence favored a predominant association of ligand with dendrites of intrinsic striatal neurons: (i) the high frequency with which labeled interfaces implicated a dendrite, (ii) the enrichment of dendro-dendritic interfaces, and (iii) the occurrence of dendritic profiles labeled at several contact points along their plasma membranes. A small proportion of labeled sites was associated with axo-axonic interfaces, which may subserve the kappa opioid-induced regulation of presynaptic dopamine and acetylcholine release documented in guinea pig neostriatum. Although most membrane-associated kappa sites were found at extrasynaptic locations, approximately 23% were associated with synaptic specializations. This proportion is markedly higher than that previously reported for either mu or delta sites in rat neostriatum. Whether labeled synapses represent preferential sites of action for kappa ligands remains to be established. In any event, these results support the hypothesis that in mammalian brain kappa opioid receptors are conformationally and functionally distinct from mu and delta types.

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Selected References

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  1. Adamson P., Xiang J. Z., Mantzourides T., Brammer M. J., Campbell I. C. Presynaptic alpha 2-adrenoceptor and kappa-opiate receptor occupancy promotes closure of neuronal (N-type) calcium channels. Eur J Pharmacol. 1989 Dec 12;174(1):63–70. doi: 10.1016/0014-2999(89)90874-1. [DOI] [PubMed] [Google Scholar]
  2. Anderson K. D., Reiner A. Extensive co-occurrence of substance P and dynorphin in striatal projection neurons: an evolutionarily conserved feature of basal ganglia organization. J Comp Neurol. 1990 May 15;295(3):339–369. doi: 10.1002/cne.902950302. [DOI] [PubMed] [Google Scholar]
  3. Attali B., Saya D., Nah S. Y., Vogel Z. Kappa opiate agonists inhibit Ca2+ influx in rat spinal cord-dorsal root ganglion cocultures. Involvement of a GTP-binding protein. J Biol Chem. 1989 Jan 5;264(1):347–353. [PubMed] [Google Scholar]
  4. Bolam J. P., Somogyi P., Takagi H., Fodor I., Smith A. D. Localization of substance P-like immunoreactivity in neurons and nerve terminals in the neostriatum of the rat: a correlated light and electron microscopic study. J Neurocytol. 1983 Apr;12(2):325–344. doi: 10.1007/BF01148468. [DOI] [PubMed] [Google Scholar]
  5. Bowen W. D., Gentleman S., Herkenham M., Pert C. B. Interconverting mu and delta forms of the opiate receptor in rat striatal patches. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4818–4822. doi: 10.1073/pnas.78.8.4818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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. 1979 Jul;16(1):91–104. [PubMed] [Google Scholar]
  7. Chavkin C., James I. F., Goldstein A. Dynorphin is a specific endogenous ligand of the kappa opioid receptor. Science. 1982 Jan 22;215(4531):413–415. doi: 10.1126/science.6120570. [DOI] [PubMed] [Google Scholar]
  8. Cherubini E., North R. A. Mu and kappa opioids inhibit transmitter release by different mechanisms. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1860–1863. doi: 10.1073/pnas.82.6.1860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Corbett A. D., Paterson S. J., McKnight A. T., Magnan J., Kosterlitz H. W. Dynorphin and dynorphin are ligands for the kappa-subtype of opiate receptor. Nature. 1982 Sep 2;299(5878):79–81. doi: 10.1038/299079a0. [DOI] [PubMed] [Google Scholar]
  10. Dana C., Vial M., Leonard K., Beauregard A., Kitabgi P., Vincent J. P., Rostène W., Beaudet A. Electron microscopic localization of neurotensin binding sites in the midbrain tegmentum of the rat. I. Ventral tegmental area and the interfascicular nucleus. J Neurosci. 1989 Jul;9(7):2247–2257. doi: 10.1523/JNEUROSCI.09-07-02247.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Demoliou-Mason C. D., Barnard E. A. Distinct subtypes of the opioid receptor with allosteric interactions in brain membranes. J Neurochem. 1986 Apr;46(4):1118–1128. doi: 10.1111/j.1471-4159.1986.tb00626.x. [DOI] [PubMed] [Google Scholar]
  12. Fallon J. H., Leslie F. M., Cone R. I. Dynorphin-containing pathways in the substantia nigra and ventral tegmentum: a double labeling study using combined immunofluorescence and retrograde tracing. Neuropeptides. 1985 Feb;5(4-6):457–460. doi: 10.1016/0143-4179(85)90053-8. [DOI] [PubMed] [Google Scholar]
  13. Fallon J. H., Leslie F. M. Distribution of dynorphin and enkephalin peptides in the rat brain. J Comp Neurol. 1986 Jul 15;249(3):293–336. doi: 10.1002/cne.902490302. [DOI] [PubMed] [Google Scholar]
  14. Foote R. W., Maurer R. Autoradiographic localization of opiate kappa-receptors in the guinea-pig brain. Eur J Pharmacol. 1982 Nov 5;85(1):99–103. doi: 10.1016/0014-2999(82)90429-0. [DOI] [PubMed] [Google Scholar]
  15. Foote R. W., Maurer R. Opioid binding sites in the nigrostriatal system of the guinea pig are not located on nigral dopaminergic neurons. Neurosci Lett. 1986 Apr 24;65(3):341–345. doi: 10.1016/0304-3940(86)90286-7. [DOI] [PubMed] [Google Scholar]
  16. Gairin J. E., Gouarderes C., Mazarguil H., Alvinerie P., Cros J. [D-Pro10]Dynorphin-(1-11) is a highly potent and selective ligand for kappa opioid receptors. Eur J Pharmacol. 1984 Nov 13;106(2):457–458. doi: 10.1016/0014-2999(84)90741-6. [DOI] [PubMed] [Google Scholar]
  17. Gairin J. E., Jomary C., Pradayrol L., Cros J., Meunier J. C. 125I-DPDYN, monoiodo[D-Pro10]dynorphin(1-11): a highly radioactive and selective probe for the study of kappa opioid receptors. Biochem Biophys Res Commun. 1986 Feb 13;134(3):1142–1150. doi: 10.1016/0006-291x(86)90370-0. [DOI] [PubMed] [Google Scholar]
  18. Gerfen C. R., Young W. S., 3rd Distribution of striatonigral and striatopallidal peptidergic neurons in both patch and matrix compartments: an in situ hybridization histochemistry and fluorescent retrograde tracing study. Brain Res. 1988 Sep 13;460(1):161–167. doi: 10.1016/0006-8993(88)91217-6. [DOI] [PubMed] [Google Scholar]
  19. Gilbert P. E., Martin W. R. The effects of morphine and nalorphine-like drugs in the nondependent, morphine-dependent and cyclazocine-dependent chronic spinal dog. J Pharmacol Exp Ther. 1976 Jul;198(1):66–82. [PubMed] [Google Scholar]
  20. Goodman R. R., Snyder S. H. Kappa opiate receptors localized by autoradiography to deep layers of cerebral cortex: relation to sedative effects. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5703–5707. doi: 10.1073/pnas.79.18.5703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Goodman R. R., Snyder S. H., Kuhar M. J., Young W. S., 3rd Differentiation of delta and mu opiate receptor localizations by light microscopic autoradiography. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6239–6243. doi: 10.1073/pnas.77.10.6239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Greenwood N. D., Guppy I. W., Simmons H. P. The direct gas chromatographic analysis of barbiturates as their sodium salts. J Chromatogr Sci. 1975 Aug 10;13(8):349–354. doi: 10.1093/chromsci/13.8.349. [DOI] [PubMed] [Google Scholar]
  23. Hamel E., Beaudet A. Electron microscopic autoradiographic localization of opioid receptors in rat neostriatum. Nature. 1984 Nov 8;312(5990):155–157. doi: 10.1038/312155a0. [DOI] [PubMed] [Google Scholar]
  24. Hamel E., Beaudet A. Opioid receptors in rat neostriatum: radioautographic distribution at the electron microscopic level. Brain Res. 1987 Jan 20;401(2):239–257. doi: 10.1016/0006-8993(87)91409-0. [DOI] [PubMed] [Google Scholar]
  25. Herkenham M. Mismatches between neurotransmitter and receptor localizations in brain: observations and implications. Neuroscience. 1987 Oct;23(1):1–38. doi: 10.1016/0306-4522(87)90268-5. [DOI] [PubMed] [Google Scholar]
  26. Huffman R. D., Frey J. M. Response of rat globus pallidus neurons to microintophoretically applied mu and kappa opioid receptor agonists. Eur J Pharmacol. 1989 Nov 7;170(3):179–191. doi: 10.1016/0014-2999(89)90538-4. [DOI] [PubMed] [Google Scholar]
  27. Itzhak Y., Hiller J. M., Simon E. J. Solubilization and characterization of mu, delta, and kappa opioid binding sites from guinea pig brain: physical separation of kappa receptors. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4217–4221. doi: 10.1073/pnas.81.13.4217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Jomary C., Gairin J. E., Cros J., Meunier J. C. Autoradiographic localization of supraspinal kappa-opioid receptors with [125I-Tyr1, D-Pro10]dynorphin A-(1-11). Proc Natl Acad Sci U S A. 1988 Jan;85(2):627–631. doi: 10.1073/pnas.85.2.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kita H., Kitai S. T. Glutamate decarboxylase immunoreactive neurons in rat neostriatum: their morphological types and populations. Brain Res. 1988 May 3;447(2):346–352. doi: 10.1016/0006-8993(88)91138-9. [DOI] [PubMed] [Google Scholar]
  30. Kosterlitz H. W., Paterson S. J., Robson L. E. Characterization of the kappa-subtype of the opiate receptor in the guinea-pig brain. Br J Pharmacol. 1981 Aug;73(4):939–949. doi: 10.1111/j.1476-5381.1981.tb08749.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lahti R. A., Mickelson M. M., Jodelis K. S., McCall J. M. Comparative neuroanatomical distribution of the kappa and mu opioid receptors in guinea pig brain sections. Eur J Pharmacol. 1989 Aug 3;166(3):563–566. doi: 10.1016/0014-2999(89)90377-4. [DOI] [PubMed] [Google Scholar]
  32. Lapchak P. A., Araujo D. M., Collier B. Regulation of endogenous acetylcholine release from mammalian brain slices by opiate receptors: hippocampus, striatum and cerebral cortex of guinea-pig and rat. Neuroscience. 1989;31(2):313–325. doi: 10.1016/0306-4522(89)90376-x. [DOI] [PubMed] [Google Scholar]
  33. Lord J. A., Waterfield A. A., Hughes J., Kosterlitz H. W. Endogenous opioid peptides: multiple agonists and receptors. Nature. 1977 Jun 9;267(5611):495–499. doi: 10.1038/267495a0. [DOI] [PubMed] [Google Scholar]
  34. 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. 1987 Aug;7(8):2445–2464. [PMC free article] [PubMed] [Google Scholar]
  35. Marcel D., Pollard H., Verroust P., Schwartz J. C., Beaudet A. Electron microscopic localization of immunoreactive enkephalinase (EC 3.4.24.11) in the neostriatum of the rat. J Neurosci. 1990 Aug;10(8):2804–2817. doi: 10.1523/JNEUROSCI.10-08-02804.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Martin W. R., Eades C. G., Thompson J. A., Huppler R. E., Gilbert P. E. The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther. 1976 Jun;197(3):517–532. [PubMed] [Google Scholar]
  37. Mulder A. H., Wardeh G., Hogenboom F., Frankhuyzen A. L. Kappa- and delta-opioid receptor agonists differentially inhibit striatal dopamine and acetylcholine release. Nature. 1984 Mar 15;308(5956):278–280. doi: 10.1038/308278a0. [DOI] [PubMed] [Google Scholar]
  38. Neal C. R., Jr, Newman S. W. Prodynorphin peptide distribution in the forebrain of the Syrian hamster and rat: a comparative study with antisera against dynorphin A, dynorphin B, and the C-terminus of the prodynorphin precursor molecule. J Comp Neurol. 1989 Oct 15;288(3):353–386. doi: 10.1002/cne.902880302. [DOI] [PubMed] [Google Scholar]
  39. North R. A., Williams J. T., Surprenant A., Christie M. J. Mu and delta receptors belong to a family of receptors that are coupled to potassium channels. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5487–5491. doi: 10.1073/pnas.84.15.5487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Periyasamy S., Hoss W. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain. Life Sci. 1990;47(3):219–225. doi: 10.1016/0024-3205(90)90323-j. [DOI] [PubMed] [Google Scholar]
  41. Riesenberg R., Nitsch C. Two different types of dynorphin-A-immunoreactive terminals in rat substantia nigra. Cell Tissue Res. 1990 Jul;261(1):107–113. doi: 10.1007/BF00329443. [DOI] [PubMed] [Google Scholar]
  42. Schmitt F. O. Molecular regulators of brain function: a new view. Neuroscience. 1984 Dec;13(4):991–1001. doi: 10.1016/0306-4522(84)90283-5. [DOI] [PubMed] [Google Scholar]
  43. 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. 1989 May-Jun;10(3):499–522. doi: 10.1016/0196-9781(89)90135-6. [DOI] [PubMed] [Google Scholar]
  44. Sharif N. A., Hunter J. C., Hill R. G., Hughes J. [125I]dynorphin(1-8) produces a similar pattern of kappa-opioid receptor labelling to [3H]dynorphin(1-8) and [3H]etorphine in guinea pig brain: a quantitative autoradiographic study. Neurosci Lett. 1988 Apr 12;86(3):272–278. doi: 10.1016/0304-3940(88)90495-8. [DOI] [PubMed] [Google Scholar]
  45. Szigethy E., Leonard K., Beaudet A. Ultrastructural localization of [125I]neurotensin binding sites to cholinergic neurons of the rat nucleus basalis magnocellularis. Neuroscience. 1990;36(2):377–391. doi: 10.1016/0306-4522(90)90433-5. [DOI] [PubMed] [Google Scholar]
  46. Tempel A., Zukin R. S. Neuroanatomical patterns of the mu, delta, and kappa opioid receptors of rat brain as determined by quantitative in vitro autoradiography. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4308–4312. doi: 10.1073/pnas.84.12.4308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Vincent S. R., Hökfelt T., Christensson I., Terenius L. Dynorphin-immunoreactive neurons in the central nervous system of the rat. Neurosci Lett. 1982 Nov 30;33(2):185–190. doi: 10.1016/0304-3940(82)90249-x. [DOI] [PubMed] [Google Scholar]
  48. Wagner J. J., Evans C. J., Chavkin C. Focal stimulation of the mossy fibers releases endogenous dynorphins that bind kappa 1-opioid receptors in guinea pig hippocampus. J Neurochem. 1991 Jul;57(1):333–343. doi: 10.1111/j.1471-4159.1991.tb02132.x. [DOI] [PubMed] [Google Scholar]
  49. Waksman G., Hamel E., Fournié-Zaluski M. C., Roques B. P. Autoradiographic comparison of the distribution of the neutral endopeptidase "enkephalinase" and of mu and delta opioid receptors in rat brain. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1523–1527. doi: 10.1073/pnas.83.5.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Werling L. L., Frattali A., Portoghese P. S., Takemori A. E., Cox B. M. Kappa receptor regulation of dopamine release from striatum and cortex of rats and guinea pigs. J Pharmacol Exp Ther. 1988 Jul;246(1):282–286. [PubMed] [Google Scholar]
  51. Zamir N., Palkovits M., Brownstein M. J. Distribution of immunoreactive dynorphin in the central nervous system of the rat. Brain Res. 1983 Nov 28;280(1):81–93. doi: 10.1016/0006-8993(83)91176-9. [DOI] [PubMed] [Google Scholar]
  52. Zamir N., Palkovits M., Weber E., Mezey E., Brownstein M. J. A dynorphinergic pathway of Leu-enkephalin production in rat substantia nigra. Nature. 1984 Feb 16;307(5952):643–645. doi: 10.1038/307643a0. [DOI] [PubMed] [Google Scholar]
  53. Zukin R. S., Eghbali M., Olive D., Unterwald E. M., Tempel A. Characterization and visualization of rat and guinea pig brain kappa opioid receptors: evidence for kappa 1 and kappa 2 opioid receptors. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4061–4065. doi: 10.1073/pnas.85.11.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]

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