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. 1987 Jun;91(2):287–297. doi: 10.1111/j.1476-5381.1987.tb10283.x

D2-dopamine receptor-mediated inhibition of intracellular Ca2+ mobilization and release of acetylcholine from guinea-pig neostriatal slices.

H Fujiwara, N Kato, H Shuntoh, C Tanaka
PMCID: PMC1853530  PMID: 2886167

Abstract

The effect of dopamine receptor activation on electrically- or high K+ (30 mM)-evoked neurotransmitter release and rise in intracellular Ca2+ concentration was investigated using slices of guinea-pig neostriatum. A specific D2-dopamine receptor agonist, LY-171555 (a laevorotatory enantiomer of LY-141865: N-propyl tricyclic pyrazole) at 10(-6) M inhibited electrical stimulation- and high K+-evoked release of [3H]-acetylcholine ([3H]-ACh) to 47.7 +/- 6.0% and 54.1 +/- 5.0% of control, respectively. The maximal inhibition by LY-171555 at 10(-5) M was 54.8 +/- 5.1% reduction of the control. The half-maximal effective concentration (EC50) of LY-171555 for the inhibition of [3H]-ACh release was 2.3 X 10(-7) M. A specific D2-dopamine receptor antagonist, (-)-sulpiride (10(-7) M) reversed the inhibition of [3H]-ACh release induced by LY-171555. A specific D1-dopamine receptor agonist, SK&F 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-benzazepine) (10(-5) M) had no effect on the release of [3H]-ACh. LY-171555 (10(-6) M) also inhibited the high K+-evoked endogenous glutamate release, by 47% of control. This inhibitory effect was reversed by (-)-sulpiride (10(-7) M). We used a fluorescent, highly selective Ca2+ indicator, 'quin 2' to measure intracellular free Ca2+ concentrations ([Ca2+]i). Electrical stimulation of slices preloaded with quin 2 led to an elevation of relative fluorescence intensity and this response was reduced by the removal of Ca2+ from the bathing medium. These results indicate that the enhanced elevation in fluorescence intensity in the quin 2-loaded slices reflects the increase of intracellular free Ca2+ concentration, [Ca2+]i. The mixed D1- and D2-receptor agonist, apomorphine and LY-171555 inhibited the increase of [Ca2+]i induced by electrical stimulation or high K+ medium, in a concentration-dependent manner, while SK&F 38393 did not affect the increase of [Ca2+]i. The maximal inhibitory effect of LY-171555 at 3 X 10(-5) M was 35 +/- 3% reduction in control values. The inhibitory effect of LY-171555 was antagonized by (-)-sulpiride (10(-7) M). There was a high correlation (r = 0.997, P less than 0.05) between the D 2-receptor-mediated inhibition of the stimulated rise of [Ca2+]i and [3H]-ACh release. When the slices were superfused with the Ca2+-free medium containing EGTA (10(-4) M) for 5 min, the rise in [Ca2+]i was markedly suppressed to 18.0% of control by LY-171555 (10(-6) M). These data indicate that activation of the D2-dopamine receptor suppresses the elevation of [Ca2+]i induced by depolarizing stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Alberts P., Bartfai T., Stjärne L. Site(s) and ionic basis of alpha-autoinhibition and facilitation of "3H'noradrenaline secretion in guinea-pig vas deferens. J Physiol. 1981 Mar;312:297–334. doi: 10.1113/jphysiol.1981.sp013630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alberts P., Bartfai T., Stjärne L. The effects of atropine on [3H]acetylcholine secretion from guinea-pig myenteric plexus evoked electrically or by high potassium. J Physiol. 1982 Aug;329:93–112. doi: 10.1113/jphysiol.1982.sp014292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arbilla S., Langer S. Z. Stereoselectivity of presynaptic autoreceptors modulating dopamine release. Eur J Pharmacol. 1981 Dec 17;76(4):345–351. doi: 10.1016/0014-2999(81)90105-9. [DOI] [PubMed] [Google Scholar]
  4. Ashley R. H., Brammer M. J., Marchbanks R. Measurement of intrasynaptosomal free calcium by using the fluorescent indicator quin-2. Biochem J. 1984 Apr 1;219(1):149–158. doi: 10.1042/bj2190149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baud P., Arbilla S., Langer S. Z. Inhibition of the electrically evoked release of [3H]acetylcholine in rat striatal slices: an experimental model for drugs that enhance dopaminergic neurotransmission. J Neurochem. 1985 Feb;44(2):331–337. doi: 10.1111/j.1471-4159.1985.tb05421.x. [DOI] [PubMed] [Google Scholar]
  6. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  7. Blaustein M. P., Johnson E. M., Jr, Needleman P. Calcium-dependent norepinephrine release from presynaptic nerve endings in vitro. Proc Natl Acad Sci U S A. 1972 Aug;69(8):2237–2240. doi: 10.1073/pnas.69.8.2237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Canonico P. L., Valdenegro C. A., Macleod R. M. Dopamine inhibits 32P incorporation into phosphatidylinositol in the anterior pituitary gland of the rat. Endocrinology. 1982 Jul;111(1):347–349. doi: 10.1210/endo-111-1-347. [DOI] [PubMed] [Google Scholar]
  9. Cubeddu L. X., Hoffmann I. S. Frequency-dependent release of acetylcholine and dopamine from rabbit striatum: its modulation by dopaminergic receptors. J Neurochem. 1983 Jul;41(1):94–101. doi: 10.1111/j.1471-4159.1983.tb11818.x. [DOI] [PubMed] [Google Scholar]
  10. Cubeddu L. X., Hoffmann I. S. Operational characteristics of the inhibitory feedback mechanism for regulation of dopamine release via presynaptic receptors. J Pharmacol Exp Ther. 1982 Nov;223(2):497–501. [PubMed] [Google Scholar]
  11. Di Virgilio F., Lew D. P., Pozzan T. Protein kinase C activation of physiological processes in human neutrophils at vanishingly small cytosolic Ca2+ levels. Nature. 1984 Aug 23;310(5979):691–693. doi: 10.1038/310691a0. [DOI] [PubMed] [Google Scholar]
  12. Dufy B., Vincent J. D., Fleury H., Du Pasquier P., Gourdji D., Tixier-Vidal A. Dopamine inhibition of action potentials in a prolactin secreting cell line is modulated by oestrogen. Nature. 1979 Dec 20;282(5741):855–857. doi: 10.1038/282855a0. [DOI] [PubMed] [Google Scholar]
  13. Hallam T. J., Thompson N. T., Scrutton M. C., Rink T. J. The role of cytoplasmic free calcium in the responses of quin2-loaded human platelets to vasopressin. Biochem J. 1984 Aug 1;221(3):897–901. doi: 10.1042/bj2210897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Iversen L. L., Mitchell J. F., Srinivasan V. The release of gamma-aminobutyric acid during inhibition in the cat visual cortex. J Physiol. 1971 Jan;212(2):519–534. doi: 10.1113/jphysiol.1971.sp009339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lehmann J., Briley M., Langer S. Z. Characterization of dopamine autoreceptor and [3H]spiperone binding sites in vitro with classical and novel dopamine receptor agonists. Eur J Pharmacol. 1983 Mar 18;88(1):11–26. doi: 10.1016/0014-2999(83)90387-4. [DOI] [PubMed] [Google Scholar]
  16. Meldolesi J., Huttner W. B., Tsien R. Y., Pozzan T. Free cytoplasmic Ca2+ and neurotransmitter release: studies on PC12 cells and synaptosomes exposed to alpha-latrotoxin. Proc Natl Acad Sci U S A. 1984 Jan;81(2):620–624. doi: 10.1073/pnas.81.2.620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Miledi R., Parker I. Calcium transients recorded with arsenazo III in the presynaptic terminal of the squid giant synapse. Proc R Soc Lond B Biol Sci. 1981 May 22;212(1187):197–211. doi: 10.1098/rspb.1981.0034. [DOI] [PubMed] [Google Scholar]
  18. Mitchell P. R., Doggett N. S. Modulation of striatal [3H]-glutamic acid release by dopaminergic drugs. Life Sci. 1980 Jun 16;26(24):2073–2081. doi: 10.1016/0024-3205(80)90592-5. [DOI] [PubMed] [Google Scholar]
  19. Narahashi T. Chemicals as tools in the study of excitable membranes. Physiol Rev. 1974 Oct;54(4):813–889. doi: 10.1152/physrev.1974.54.4.813. [DOI] [PubMed] [Google Scholar]
  20. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  21. Nitsch C., Kim J. K., Shimada C., Okada Y. Effect of hippocampus extirpation in the rat on glutamate levels in target structures of hippocampal efferents. Neurosci Lett. 1979 Mar;11(3):295–299. doi: 10.1016/0304-3940(79)90011-9. [DOI] [PubMed] [Google Scholar]
  22. Rorsman P., Abrahamsson H., Gylfe E., Hellman B. Dual effects of glucose on the cytosolic Ca2+ activity of mouse pancreatic beta-cells. FEBS Lett. 1984 May 7;170(1):196–200. doi: 10.1016/0014-5793(84)81398-8. [DOI] [PubMed] [Google Scholar]
  23. Rowlands G. J., Roberts P. J. Specific calcium-dependent release of endogenous glutamate from rat striatum is reduced by destruction of the cortico-striatal tract. Exp Brain Res. 1980;39(2):239–240. doi: 10.1007/BF00237555. [DOI] [PubMed] [Google Scholar]
  24. Saijoh K., Fujiwara H., Tanaka C. Influence of hypoxia on release and uptake of neurotransmitters in guinea pig striatal slices: dopamine and acetylcholine. Jpn J Pharmacol. 1985 Dec;39(4):529–539. doi: 10.1254/jjp.39.529. [DOI] [PubMed] [Google Scholar]
  25. Scatton B. Effect of dopamine agonists and neuroleptic agents on striatal acetylcholine transmission in the rat: evidence against dopamine receptor multiplicity. J Pharmacol Exp Ther. 1982 Jan;220(1):197–202. [PubMed] [Google Scholar]
  26. Schofield J. G. Use of a trapped fluorescent indicator to demonstrate effects of thyroliberin and dopamine on cytoplasmic calcium concentrations in bovine anterior pituitary cells. FEBS Lett. 1983 Aug 8;159(1-2):79–82. doi: 10.1016/0014-5793(83)80420-7. [DOI] [PubMed] [Google Scholar]
  27. Stoof J. C., Kebabian J. W. Independent in vitro regulation by the D-2 dopamine receptor of dopamine-stimulated efflux of cyclic AMP and K+-stimulated release of acetylcholine from rat neostriatum. Brain Res. 1982 Nov 4;250(2):263–270. doi: 10.1016/0006-8993(82)90420-6. [DOI] [PubMed] [Google Scholar]
  28. Tanaka C., Fujiwara H., Fujii Y. Acetylcholine release from guinea pig caudate slices evoked by phorbol ester and calcium. FEBS Lett. 1986 Jan 20;195(1-2):129–134. doi: 10.1016/0014-5793(86)80146-6. [DOI] [PubMed] [Google Scholar]
  29. Tsien R. Y., Pozzan T., Rink T. J. Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J Cell Biol. 1982 Aug;94(2):325–334. doi: 10.1083/jcb.94.2.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tsien R. Y., Pozzan T., Rink T. J. T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes. Nature. 1982 Jan 7;295(5844):68–71. doi: 10.1038/295068a0. [DOI] [PubMed] [Google Scholar]

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