Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Nov;113(3):815–822. doi: 10.1111/j.1476-5381.1994.tb17066.x

Evidence for P2-purinoceptor-mediated inhibition of noradrenaline release in rat brain cortex.

I von Kügelgen 1, L Späth 1, K Starke 1
PMCID: PMC1510427  PMID: 7858872

Abstract

1. Some postganglionic sympathetic axons possess P2Y-like P2-purinoceptors which, when activated, decrease the release of noradrenaline. We examined the question of whether such receptors also occur at the noradrenergic axons in the rat brain cortex. Slices of the brain cortex were preincubated with [3H]-noradrenaline, then superfused with medium containing desipramine (1 microM) and stimulated electrically, in most experiments by trains of 4 pulses/100 Hz. 2. The selective adenosine A1-receptor agonist, N6-cyclopentyl-adenosine (CPA; 0.03-3 microM) as well as the non-subtype-selective agonist 5'-N-ethylcarboxamido-adenosine (NECA; 0.3-3 microM) reduced the evoked overflow of tritium, whereas the adenosine A2a-receptor agonist, 2-p-(2-carbonylethyl)-phenethylamino-5'-N-ethylcarboxamido-a denosine (CGS-21680; 0.003-30 microM) and the adenosine A3-receptor agonist N6-2-(4-aminophenyl)ethyl-adenosine (APNEA; 0.03-3 microM) caused no change. Of the nucleotides tested, ATP (30-300 microM), adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S; 30-300 microM), adenosine-5'-O-(2-thiodiphosphate) (ADP beta S; 30-300 microM), P1,P4-di(adenosine-5')-tetraphosphate (Ap4A; 30-300 microM) and the preferential P2Y-purinoceptor agonist, 2-methylthio-ATP (300 microM) decreased the evoked overflow of tritium. The P2X-purinoceptor agonist, alpha,beta-methylene-ATP (3-300 microM) caused no change. 3. The A1-selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 10 nM) attenuated the effects of the nucleosides CPA (apparent pKB value 9.8) and NECA as well as of the nucleotides ATP (apparent pKB 9.3), ATP gamma S (apparent pKB 9.2) and ADP beta S (apparent pKB 8.7).(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
815

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bailey S. J., Hickman D., Hourani S. M. Characterization of the P1-purinoceptors mediating contraction of the rat colon muscularis mucosae. Br J Pharmacol. 1992 Feb;105(2):400–404. doi: 10.1111/j.1476-5381.1992.tb14265.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnard E. A., Burnstock G., Webb T. E. G protein-coupled receptors for ATP and other nucleotides: a new receptor family. Trends Pharmacol Sci. 1994 Mar;15(3):67–70. doi: 10.1016/0165-6147(94)90280-1. [DOI] [PubMed] [Google Scholar]
  3. Boland B., Himpens B., Vincent M. F., Gillis J. M., Casteels R. ATP activates P2x-contracting and P2y-relaxing purinoceptors in the smooth muscle of mouse vas deferens. Br J Pharmacol. 1992 Dec;107(4):1152–1158. doi: 10.1111/j.1476-5381.1992.tb13422.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown S. J., James S., Reddington M., Richardson P. J. Both A1 and A2a purine receptors regulate striatal acetylcholine release. J Neurochem. 1990 Jul;55(1):31–38. doi: 10.1111/j.1471-4159.1990.tb08817.x. [DOI] [PubMed] [Google Scholar]
  5. Bruns R. F. Adenosine receptor activation by adenine nucleotides requires conversion of the nucleotides to adenosine. Naunyn Schmiedebergs Arch Pharmacol. 1980;315(1):5–13. doi: 10.1007/BF00504224. [DOI] [PubMed] [Google Scholar]
  6. Bruns R. F., Fergus J. H., Badger E. W., Bristol J. A., Santay L. A., Hartman J. D., Hays S. J., Huang C. C. Binding of the A1-selective adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes. Naunyn Schmiedebergs Arch Pharmacol. 1987 Jan;335(1):59–63. doi: 10.1007/BF00165037. [DOI] [PubMed] [Google Scholar]
  7. Burnstock G., Warland J. J. P2-purinoceptors of two subtypes in the rabbit mesenteric artery: reactive blue 2 selectively inhibits responses mediated via the P2y-but not the P2x-purinoceptor. Br J Pharmacol. 1987 Feb;90(2):383–391. doi: 10.1111/j.1476-5381.1987.tb08968.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Craig C. G., White T. D. Low-level N-methyl-D-aspartate receptor activation provides a purinergic inhibitory threshold against further N-methyl-D-aspartate-mediated neurotransmission in the cortex. J Pharmacol Exp Ther. 1992 Mar;260(3):1278–1284. [PubMed] [Google Scholar]
  9. Cunha R. A., Ribeiro J. A., Sebastião A. M. Purinergic modulation of the evoked release of [3H]acetylcholine from the hippocampus and cerebral cortex of the rat: role of the ectonucleotidases. Eur J Neurosci. 1994 Jan 1;6(1):33–42. doi: 10.1111/j.1460-9568.1994.tb00245.x. [DOI] [PubMed] [Google Scholar]
  10. De Mey J., Burnstock G., Vanhoutte P. M. Modulation of the evoked release of noradrenaline in canine saphenous vein via presynaptic receptors for adenosine but not ATP. Eur J Pharmacol. 1979 May 15;55(4):401–405. doi: 10.1016/0014-2999(79)90115-8. [DOI] [PubMed] [Google Scholar]
  11. Dunn P. M., Blakeley A. G. Suramin: a reversible P2-purinoceptor antagonist in the mouse vas deferens. Br J Pharmacol. 1988 Feb;93(2):243–245. doi: 10.1111/j.1476-5381.1988.tb11427.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fischer B., Boyer J. L., Hoyle C. H., Ziganshin A. U., Brizzolara A. L., Knight G. E., Zimmet J., Burnstock G., Harden T. K., Jacobson K. A. Identification of potent, selective P2Y-purinoceptor agonists: structure-activity relationships for 2-thioether derivatives of adenosine 5'-triphosphate. J Med Chem. 1993 Nov 26;36(24):3937–3946. doi: 10.1021/jm00076a023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Forsyth K. M., Bjur R. A., Westfall D. P. Nucleotide modulation of norepinephrine release from sympathetic nerves in the rat vas deferens. J Pharmacol Exp Ther. 1991 Mar;256(3):821–826. [PubMed] [Google Scholar]
  14. Fredholm B. B., Dunwiddie T. V. How does adenosine inhibit transmitter release? Trends Pharmacol Sci. 1988 Apr;9(4):130–134. doi: 10.1016/0165-6147(88)90194-0. [DOI] [PubMed] [Google Scholar]
  15. Fredholm B. B. Vascular and metabolic effects of theophylline, dibuturyl cyclic AMP and dibuturyl cyclic GMP in canine subcutaneous adipose tissue in situ. Acta Physiol Scand. 1974 Jan;90(1):226–236. doi: 10.1111/j.1748-1716.1974.tb05581.x. [DOI] [PubMed] [Google Scholar]
  16. Fuder H., Brink A., Meincke M., Tauber U. Purinoceptor-mediated modulation by endogenous and exogenous agonists of stimulation-evoked [3H]noradrenaline release on rat iris. Naunyn Schmiedebergs Arch Pharmacol. 1992 Apr;345(4):417–423. doi: 10.1007/BF00176619. [DOI] [PubMed] [Google Scholar]
  17. Fuder H., Muth U. ATP and endogenous agonists inhibit evoked [3H]-noradrenaline release in rat iris via A1 and P2y-like purinoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1993 Oct;348(4):352–357. doi: 10.1007/BF00171333. [DOI] [PubMed] [Google Scholar]
  18. Gonçalves J., Queiroz G. Facilitatory and inhibitory modulation by endogenous adenosine of noradrenaline release in the epididymal portion of rat vas deferens. Naunyn Schmiedebergs Arch Pharmacol. 1993 Oct;348(4):367–371. doi: 10.1007/BF00171335. [DOI] [PubMed] [Google Scholar]
  19. Grimm U., Fuder H., Moser U., Bümert H. G., Mutschler E., Lambrecht G. Characterization of the prejunctional muscarinic receptors mediating inhibition of evoked release of endogenous noradrenaline in rabbit isolated vas deferens. Naunyn Schmiedebergs Arch Pharmacol. 1994 Jan;349(1):1–10. doi: 10.1007/BF00178199. [DOI] [PubMed] [Google Scholar]
  20. Harms H. H., Wardeh G., Mulder A. H. Adenosine modulates depolarization-induced release of 3H-noradrenaline from slices of rat brain neocortex. Eur J Pharmacol. 1978 Jun 1;49(3):305–308. doi: 10.1016/0014-2999(78)90107-3. [DOI] [PubMed] [Google Scholar]
  21. Hedqvist P., Fredholm B. B. Effects of adenosine on adrenergic neurotransmission; prejunctional inhibition and postjunctional enhancement. Naunyn Schmiedebergs Arch Pharmacol. 1976 Jun;293(3):217–223. doi: 10.1007/BF00507344. [DOI] [PubMed] [Google Scholar]
  22. Houston D. A., Burnstock G., Vanhoutte P. M. Different P2-purinergic receptor subtypes of endothelium and smooth muscle in canine blood vessels. J Pharmacol Exp Ther. 1987 May;241(2):501–506. [PubMed] [Google Scholar]
  23. Hoyle C. H., Knight G. E., Burnstock G. Suramin antagonizes responses to P2-purinoceptor agonists and purinergic nerve stimulation in the guinea-pig urinary bladder and taenia coli. Br J Pharmacol. 1990 Mar;99(3):617–621. doi: 10.1111/j.1476-5381.1990.tb12979.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Illes P., Nörenberg W. Neuronal ATP receptors and their mechanism of action. Trends Pharmacol Sci. 1993 Feb;14(2):50–54. doi: 10.1016/0165-6147(93)90030-n. [DOI] [PubMed] [Google Scholar]
  25. Jackisch R., Fehr R., Hertting G. Adenosine: an endogenous modulator of hippocampal noradrenaline release. Neuropharmacology. 1985 Jun;24(6):499–507. doi: 10.1016/0028-3908(85)90055-3. [DOI] [PubMed] [Google Scholar]
  26. Jackson E. K., Herzer W. A., Suzuki F. KF17837 is an A2 adenosine receptor antagonist in vivo. J Pharmacol Exp Ther. 1993 Dec;267(3):1304–1310. [PubMed] [Google Scholar]
  27. Jarvis M. F., Schulz R., Hutchison A. J., Do U. H., Sills M. A., Williams M. [3H]CGS 21680, a selective A2 adenosine receptor agonist directly labels A2 receptors in rat brain. J Pharmacol Exp Ther. 1989 Dec;251(3):888–893. [PubMed] [Google Scholar]
  28. Jonzon B., Fredholm B. B. Adenosine receptor mediated inhibition of noradrenaline release from slices of the rat hippocampus. Life Sci. 1984 Nov 5;35(19):1971–1979. doi: 10.1016/0024-3205(84)90478-8. [DOI] [PubMed] [Google Scholar]
  29. Kennedy C. P1- and P2-purinoceptor subtypes--an update. Arch Int Pharmacodyn Ther. 1990 Jan-Feb;303:30–50. [PubMed] [Google Scholar]
  30. Knowles R. G., Palacios M., Palmer R. M., Moncada S. Kinetic characteristics of nitric oxide synthase from rat brain. Biochem J. 1990 Jul 1;269(1):207–210. doi: 10.1042/bj2690207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kurz K., von Kügelgen I., Starke K. Prejunctional modulation of noradrenaline release in mouse and rat vas deferens: contribution of P1- and P2-purinoceptors. Br J Pharmacol. 1993 Dec;110(4):1465–1472. doi: 10.1111/j.1476-5381.1993.tb13986.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lohse M. J., Klotz K. N., Lindenborn-Fotinos J., Reddington M., Schwabe U., Olsson R. A. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX)--a selective high affinity antagonist radioligand for A1 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1987 Aug;336(2):204–210. doi: 10.1007/BF00165806. [DOI] [PubMed] [Google Scholar]
  33. Lukacsko P., Blumberg A. Modulation of the vasoconstrictor response to adrenergic stimulation by nucleosides and nucleotides. J Pharmacol Exp Ther. 1982 Aug;222(2):344–349. [PubMed] [Google Scholar]
  34. Miyahara H., Suzuki H. Pre- and post-junctional effects of adenosine triphosphate on noradrenergic transmission in the rabbit ear artery. J Physiol. 1987 Aug;389:423–440. doi: 10.1113/jphysiol.1987.sp016664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Moody C. J., Meghji P., Burnstock G. Stimulation of P1-purinoceptors by ATP depends partly on its conversion to AMP and adenosine and partly on direct action. Eur J Pharmacol. 1984 Jan 13;97(1-2):47–54. doi: 10.1016/0014-2999(84)90511-9. [DOI] [PubMed] [Google Scholar]
  36. Rubino A., Amerini S., Ledda F., Mantelli L. ATP modulates the efferent function of capsaicin-sensitive neurones in guinea-pig isolated atria. Br J Pharmacol. 1992 Mar;105(3):516–520. doi: 10.1111/j.1476-5381.1992.tb09011.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sebastião A. M., Stone T. W., Ribeiro J. A. The inhibitory adenosine receptor at the neuromuscular junction and hippocampus of the rat: antagonism by 1,3,8-substituted xanthines. Br J Pharmacol. 1990 Oct;101(2):453–459. doi: 10.1111/j.1476-5381.1990.tb12729.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shen K. Z., North R. A. Excitation of rat locus coeruleus neurons by adenosine 5'-triphosphate: ionic mechanism and receptor characterization. J Neurosci. 1993 Mar;13(3):894–899. doi: 10.1523/JNEUROSCI.13-03-00894.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Shimada J., Suzuki F., Nonaka H., Ishii A., Ichikawa S. (E)-1,3-dialkyl-7-methyl-8-(3,4,5-trimethoxystyryl)xanthines: potent and selective adenosine A2 antagonists. J Med Chem. 1992 Jun 12;35(12):2342–2345. doi: 10.1021/jm00090a027. [DOI] [PubMed] [Google Scholar]
  40. Shinozuka K., Bjur R. A., Westfall D. P. Characterization of prejunctional purinoceptors on adrenergic nerves of the rat caudal artery. Naunyn Schmiedebergs Arch Pharmacol. 1988 Sep;338(3):221–227. doi: 10.1007/BF00173391. [DOI] [PubMed] [Google Scholar]
  41. Shirahase H., Usui H., Shimaji H., Kurahashi K., Fujiwara M. Endothelium-independent and endothelium-dependent contractions mediated by P2X- and P2Y-purinoceptors in canine basilar arteries. J Pharmacol Exp Ther. 1991 Feb;256(2):683–688. [PubMed] [Google Scholar]
  42. Sperlagh B., Vizi E. S. Effect of presynaptic P2 receptor stimulation on transmitter release. J Neurochem. 1991 May;56(5):1466–1470. doi: 10.1111/j.1471-4159.1991.tb02039.x. [DOI] [PubMed] [Google Scholar]
  43. Starke K., Göthert M., Kilbinger H. Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev. 1989 Jul;69(3):864–989. doi: 10.1152/physrev.1989.69.3.864. [DOI] [PubMed] [Google Scholar]
  44. Starke K., Peskar B. A., Schumacher K. A., Taube H. D. Bradykinin and postganglionic sympathetic transmission. Naunyn Schmiedebergs Arch Pharmacol. 1977 Aug;299(1):23–32. doi: 10.1007/BF00508633. [DOI] [PubMed] [Google Scholar]
  45. Starke K. Presynaptic receptors. Annu Rev Pharmacol Toxicol. 1981;21:7–30. doi: 10.1146/annurev.pa.21.040181.000255. [DOI] [PubMed] [Google Scholar]
  46. Stjärne L., Astrand P. Relative pre- and postjunctional roles of noradrenaline and adenosine 5'-triphosphate as neurotransmitters of the sympathetic nerves of guinea-pig and mouse vas deferens. Neuroscience. 1985 Mar;14(3):929–946. doi: 10.1016/0306-4522(85)90155-1. [DOI] [PubMed] [Google Scholar]
  47. Stone T. W., Cusack N. J. Absence of P2-purinoceptors in hippocampal pathways. Br J Pharmacol. 1989 Jun;97(2):631–635. doi: 10.1111/j.1476-5381.1989.tb11996.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Stone T. W. Physiological roles for adenosine and adenosine 5'-triphosphate in the nervous system. Neuroscience. 1981;6(4):523–555. doi: 10.1016/0306-4522(81)90145-7. [DOI] [PubMed] [Google Scholar]
  49. Taube H. D., Starke K., Borowski E. Presynaptic receptor systems on the noradrenergic neurones of rat brain. Naunyn Schmiedebergs Arch Pharmacol. 1977 Sep;299(2):123–141. doi: 10.1007/BF00498554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Todorov L. D., Bjur R. A., Westfall D. P. Inhibitory and facilitatory effects of purines on transmitter release from sympathetic nerves. J Pharmacol Exp Ther. 1994 Feb;268(2):985–989. [PubMed] [Google Scholar]
  51. Trendelenburg A. U., Limberger N., Starke K. Presynaptic alpha 2-autoreceptors in brain cortex: alpha 2D in the rat and alpha 2A in the rabbit. Naunyn Schmiedebergs Arch Pharmacol. 1993 Jul;348(1):35–45. doi: 10.1007/BF00168534. [DOI] [PubMed] [Google Scholar]
  52. Tschöpl M., Harms L., Nörenberg W., Illes P. Excitatory effects of adenosine 5'-triphosphate on rat locus coeruleus neurones. Eur J Pharmacol. 1992 Mar 17;213(1):71–77. doi: 10.1016/0014-2999(92)90234-u. [DOI] [PubMed] [Google Scholar]
  53. Welford L. A., Cusack N. J., Hourani S. M. ATP analogues and the guinea-pig taenia coli: a comparison of the structure-activity relationships of ectonucleotidases with those of the P2-purinoceptor. Eur J Pharmacol. 1986 Oct 7;129(3):217–224. doi: 10.1016/0014-2999(86)90431-0. [DOI] [PubMed] [Google Scholar]
  54. Wiklund N. P., Gustafsson L. E., Lundin J. Pre- and postjunctional modulation of cholinergic neuroeffector transmission by adenine nucleotides. Experiments with agonist and antagonist. Acta Physiol Scand. 1985 Dec;125(4):681–691. doi: 10.1111/j.1748-1716.1985.tb07771.x. [DOI] [PubMed] [Google Scholar]
  55. Williams M., Braunwalder A., Erickson T. J. Evaluation of the binding of the A-1 selective adenosine radioligand, cyclopentyladenosine (CPA), to rat brain tissue. Naunyn Schmiedebergs Arch Pharmacol. 1986 Feb;332(2):179–183. doi: 10.1007/BF00511410. [DOI] [PubMed] [Google Scholar]
  56. Zhou Q. Y., Li C., Olah M. E., Johnson R. A., Stiles G. L., Civelli O. Molecular cloning and characterization of an adenosine receptor: the A3 adenosine receptor. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7432–7436. doi: 10.1073/pnas.89.16.7432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Zier G., Drobny H., Valenta B., Singer E. A. Evidence against a functional link between noradrenaline uptake mechanisms and presynaptic alpha-2 adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1988 Jan;337(1):118–121. doi: 10.1007/BF00169488. [DOI] [PubMed] [Google Scholar]
  58. von Kügelgen I., Kurz K., Starke K. Axon terminal P2-purinoceptors in feedback control of sympathetic transmitter release. Neuroscience. 1993 Sep;56(2):263–267. doi: 10.1016/0306-4522(93)90330-i. [DOI] [PubMed] [Google Scholar]
  59. von Kügelgen I., Kurz K., Starke K. P2-purinoceptor-mediated autoinhibition of sympathetic transmitter release in mouse and rat vas deferens. Naunyn Schmiedebergs Arch Pharmacol. 1994 Feb;349(2):125–132. doi: 10.1007/BF00169828. [DOI] [PubMed] [Google Scholar]
  60. von Kügelgen I., Schöffel E., Starke K. Inhibition by nucleotides acting at presynaptic P2-receptors of sympathetic neuro-effector transmission in the mouse isolated vas deferens. Naunyn Schmiedebergs Arch Pharmacol. 1989 Nov;340(5):522–532. doi: 10.1007/BF00260607. [DOI] [PubMed] [Google Scholar]
  61. von Kügelgen I., Späth L., Starke K. Adenosine but not an adenine nucleotide mediates tonic purinergic inhibition, as well as inhibition by glutamate, of noradrenaline release in rabbit brain cortex slices. Naunyn Schmiedebergs Arch Pharmacol. 1992 Dec;346(6):677–684. doi: 10.1007/BF00168742. [DOI] [PubMed] [Google Scholar]
  62. von Kügelgen I., Späth L., Starke K. Stable adenine nucleotides inhibit [3H]-noradrenaline release in rabbit brain cortex slices by direct action at presynaptic adenosine A1-receptors. Naunyn Schmiedebergs Arch Pharmacol. 1992 Aug;346(2):187–196. doi: 10.1007/BF00165300. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES