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. 1987 Jul;91(3):661–669. doi: 10.1111/j.1476-5381.1987.tb11260.x

Studies on the adenosine-receptor mediating the augmentation of histamine-induced inositol phospholipid hydrolysis in guinea-pig cerebral cortex.

S J Hill, D A Kendall
PMCID: PMC1853563  PMID: 3038249

Abstract

Incubation (45 min) of slices of guinea-pig cerebral cortex with adenosine alone had no significant effect on the accumulation of [3H]-inositol phosphates but enhanced the response to histamine H1-receptor stimulation in a concentration-dependent manner. The effect of adenosine on agonist-stimulated inositol phospholipid hydrolysis appeared to be selective for histamine H1-receptor stimulation since it did not augment the phosphoinositide responses to carbachol, noradrenaline, 5-hydroxytryptamine or elevated KCl. The accumulation of [3H]-inositol phosphates induced by histamine increased linearly between 5 and 45 min incubation with agonist. However, following the simultaneous addition of histamine and adenosine, there was a marked delay in the appearance of the augmentation produced by adenosine. The augmentation of [3H]-inositol phosphate accumulation was mimicked by a number of adenosine analogues. The rank order of potency was; cyclopentyladenosine greater than R-phenyl-isopropyladenosine 5'-N-ethylcarboxamidoadenosine greater than 2-chloroadenosine. This is consistent with the order expected for an adenosine A1-receptor effect but the EC50 values were in the micro- rather than nanomolar range. The response to 2-chloroadenosine was antagonized by the xanthine adenosine-antagonists, cyclopropyltheophylline, 8-phenyltheophylline, 3-isobutyl-1-methylxanthine and theophylline, and the non-xanthine alloxazine.

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Selected References

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  1. Barberis C., Minn A., Gayet J. Adenosine transport into guinea-pig synaptosomes. J Neurochem. 1981 Feb;36(2):347–354. doi: 10.1111/j.1471-4159.1981.tb01601.x. [DOI] [PubMed] [Google Scholar]
  2. Batty I. R., Nahorski S. R., Irvine R. F. Rapid formation of inositol 1,3,4,5-tetrakisphosphate following muscarinic receptor stimulation of rat cerebral cortical slices. Biochem J. 1985 Nov 15;232(1):211–215. doi: 10.1042/bj2320211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baudry M., Evans J., Lynch G. Excitatory amino acids inhibit stimulation of phosphatidylinositol metabolism by aminergic agonists in hippocampus. Nature. 1986 Jan 23;319(6051):329–331. doi: 10.1038/319329a0. [DOI] [PubMed] [Google Scholar]
  4. Bazil C. W., Minneman K. P. An investigation of the low intrinsic activity of adenosine and its analogs at low affinity (A2) adenosine receptors in rat cerebral cortex. J Neurochem. 1986 Aug;47(2):547–553. doi: 10.1111/j.1471-4159.1986.tb04534.x. [DOI] [PubMed] [Google Scholar]
  5. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown E., Kendall D. A., Nahorski S. R. Inositol phospholipid hydrolysis in rat cerebral cortical slices: I. Receptor characterisation. J Neurochem. 1984 May;42(5):1379–1387. doi: 10.1111/j.1471-4159.1984.tb02798.x. [DOI] [PubMed] [Google Scholar]
  7. Bruns R. F., Daly J. W., Snyder S. H. Adenosine receptors in brain membranes: binding of N6-cyclohexyl[3H]adenosine and 1,3-diethyl-8-[3H]phenylxanthine. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5547–5551. doi: 10.1073/pnas.77.9.5547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bruns R. F., Lu G. H., Pugsley T. A. Characterization of the A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes. Mol Pharmacol. 1986 Apr;29(4):331–346. [PubMed] [Google Scholar]
  9. Cooper D. M., Londos C., Rodbell M. Adenosine receptor-mediated inhibition of rat cerebral cortical adenylate cyclase by a GTP-dependent process. Mol Pharmacol. 1980 Nov;18(3):598–601. [PubMed] [Google Scholar]
  10. Costa E., Guidotti A. Molecular mechanisms in the receptor action of benzodiazepines. Annu Rev Pharmacol Toxicol. 1979;19:531–545. doi: 10.1146/annurev.pa.19.040179.002531. [DOI] [PubMed] [Google Scholar]
  11. Daly J. W. Adenosine receptors: targets for future drugs. J Med Chem. 1982 Mar;25(3):197–207. doi: 10.1021/jm00345a001. [DOI] [PubMed] [Google Scholar]
  12. Daly J. W., Bruns R. F., Snyder S. H. Adenosine receptors in the central nervous system: relationship to the central actions of methylxanthines. Life Sci. 1981 May 11;28(19):2083–2097. doi: 10.1016/0024-3205(81)90614-7. [DOI] [PubMed] [Google Scholar]
  13. Daly J. W., Padgett W., Thompson R. D., Kusachi S., Bugni W. J., Olsson R. A. Structure-activity relationships for N6-substituted adenosines at a brain A1-adenosine receptor with a comparison to an A2-adenosine receptor regulating coronary blood flow. Biochem Pharmacol. 1986 Aug 1;35(15):2467–2481. doi: 10.1016/0006-2952(86)90042-0. [DOI] [PubMed] [Google Scholar]
  14. Daum P. R., Downes C. P., Young J. M. Histamine stimulation of inositol 1-phosphate accumulation in lithium-treated slices from regions of guinea pig brain. J Neurochem. 1984 Jul;43(1):25–32. doi: 10.1111/j.1471-4159.1984.tb06674.x. [DOI] [PubMed] [Google Scholar]
  15. Daum P. R., Hill S. J., Young J. M. Histamine H1-agonist potentiation of adenosine-stimulated cyclic AMP accumulation in slices of guinea-pig cerebral cortex: comparison of response and binding parameters. Br J Pharmacol. 1982 Oct;77(2):347–357. doi: 10.1111/j.1476-5381.1982.tb09304.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. DeLean A., Munson P. J., Rodbard D. Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol. 1978 Aug;235(2):E97–102. doi: 10.1152/ajpendo.1978.235.2.E97. [DOI] [PubMed] [Google Scholar]
  17. Donaldson J., Hill S. J. Enhancement of histamine H1-receptor agonist activity by 1,4-dithiothreitol in guinea-pig cerebellum and cerebral cortex. J Neurochem. 1986 Nov;47(5):1476–1482. doi: 10.1111/j.1471-4159.1986.tb00781.x. [DOI] [PubMed] [Google Scholar]
  18. Donaldson J., Hill S. J. Histamine-induced hydrolysis of polyphosphoinositides in guinea-pig ileum and brain. Eur J Pharmacol. 1986 May 27;124(3):255–265. doi: 10.1016/0014-2999(86)90226-8. [DOI] [PubMed] [Google Scholar]
  19. Donaldson J., Hill S. J. Histamine-induced inositol phospholipid breakdown in the longitudinal smooth muscle of guinea-pig ileum. Br J Pharmacol. 1985 Jun;85(2):499–512. doi: 10.1111/j.1476-5381.1985.tb08887.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Dunwiddie T. V., Fredholm B. B. Adenosine modulation of synaptic responses in rat hippocampus: possible role of inhibition or activation of adenylate cyclase. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1985;19:259–272. [PubMed] [Google Scholar]
  21. Hill S. J., Daum P., Young J. M. Affinities of histamine H1-antagonists in guinea pig brain: similarity of values determined from [3H]mepyramine binding and from inhibition of a functional response. J Neurochem. 1981 Nov;37(5):1357–1360. doi: 10.1111/j.1471-4159.1981.tb04692.x. [DOI] [PubMed] [Google Scholar]
  22. Hollingsworth E. B., Daly J. W. Accumulation of inositol phosphates and cyclic AMP in guinea-pig cerebral cortical preparations. Effects of norepinephrine, histamine, carbamylcholine and 2-chloroadenosine. Biochim Biophys Acta. 1985 Nov 20;847(2):207–216. doi: 10.1016/0167-4889(85)90022-9. [DOI] [PubMed] [Google Scholar]
  23. Hollingsworth E. B., De la Cruz R. A., Daly J. W. Accumulations of inositol phosphates and cyclic AMP in brain slices: synergistic interactions of histamine and 2-chloroadenosine. Eur J Pharmacol. 1986 Mar 11;122(1):45–50. doi: 10.1016/0014-2999(86)90156-1. [DOI] [PubMed] [Google Scholar]
  24. Kendall D. A., Nahorski S. R. 5-Hydroxytryptamine-stimulated inositol phospholipid hydrolysis in rat cerebral cortex slices: pharmacological characterization and effects of antidepressants. J Pharmacol Exp Ther. 1985 May;233(2):473–479. [PubMed] [Google Scholar]
  25. Phillis J. W., Barraco R. A. Adenosine, adenylate cyclase, and transmitter release. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1985;19:243–257. [PubMed] [Google Scholar]
  26. Sattin A., Rall T. W. The effect of adenosine and adenine nucleotides on the cyclic adenosine 3', 5'-phosphate content of guinea pig cerebral cortex slices. Mol Pharmacol. 1970 Jan;6(1):13–23. [PubMed] [Google Scholar]
  27. Schultz J., Daly J. W. Acummulation of cyclic adenosine 3', 5'-monophosphate in cerebral cortical slices from rat and mouse: stimulatory effect of alpha- and beta-adrenergic agents and adenosine. J Neurochem. 1973 Nov;21(5):1319–1326. doi: 10.1111/j.1471-4159.1973.tb07585.x. [DOI] [PubMed] [Google Scholar]
  28. Schultz J., Daly J. W. Cyclic adenosine 3',5'-monophosphate in guinea pig cerebral cortical slices. 3. Formation, degradation, and reformation of cyclic adenosine 3',5'-monophosphate during sequential stimulations by biogenic amines and adenosine. J Biol Chem. 1973 Feb 10;248(3):860–866. [PubMed] [Google Scholar]
  29. Snyder S. H. Adenosine as a neuromodulator. Annu Rev Neurosci. 1985;8:103–124. doi: 10.1146/annurev.ne.08.030185.000535. [DOI] [PubMed] [Google Scholar]
  30. van Calker D., Müller M., Hamprecht B. Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem. 1979 Nov;33(5):999–1005. doi: 10.1111/j.1471-4159.1979.tb05236.x. [DOI] [PubMed] [Google Scholar]

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