Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Jan;108(1):262–268. doi: 10.1111/j.1476-5381.1993.tb13472.x

Alpha 2-autoreceptor subclassification in rat isolated kidney by use of short trains of electrical stimulation.

C Bohmann 1, P Schollmeyer 1, L C Rump 1
PMCID: PMC1907698  PMID: 8094025

Abstract

1 Rat kidneys were perfused with Krebs-Henseleit solution and incubated with [3H]-noradrenaline. The renal nerves were electrically stimulated at either 1 Hz for 30 s or 100 Hz for 0.06 s. The stimulation induced (S-I) outflow of radioactivity was taken as an index of endogenous noradrenaline release. 2 At a frequency of 1 Hz for 30 s the alpha-adrenoceptor antagonists BRL 44408 (0.01, 0.1 microM) and imiloxan (0.1, 1.0 microM) enhanced S-I outflow of radioactivity. However, at a frequency of 100 Hz for 0.06 s the alpha-adrenoceptor antagonists, idazoxan (0.1, 1.0 microM), imiloxan (0.1, 1.0 microM), BRL 44408 (0.1, 1.0 microM), BRL 41992 (0.1, 1.0 microM) and prazosin (0.01 microM) failed to enhance S-I outflow of radioactivity. 3 Thus, the rat isolated kidney stimulated at 100 Hz for 0.06 s, avoids autoinhibition by endogenous noradrenaline and alpha-adrenoceptor antagonist affinities (pKB) at the prejunctional alpha-autoreceptor were estimated without disturbance by the endogenous activator. 4 The alpha 2-adrenoceptor agonist, clonidine, inhibited the S-I outflow of radioactivity with a maximum of 90% and an EC50 of 7.2 nM. 5 All alpha-adrenoceptor antagonists used caused parallel shifts of the concentration-response curve for clonidine to the right. The rank order of potencies was: rauwolscine (alpha 2A/B) > idazoxan (alpha 2A/B) > phentolamine (alpha 2A/B) > WB 4101 (alpha 2A) > BRL 44408 (alpha 2A) > BRL 41992 (alpha 2B) > prazosin (alpha 2B) = imiloxan (alpha 2B).(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
262

Selected References

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

  1. Alberts P. Subtype classification of the presynaptic alpha-adrenoceptors which regulate [3H]-noradrenaline secretion in guinea-pig isolated urethra. Br J Pharmacol. 1992 Jan;105(1):142–146. doi: 10.1111/j.1476-5381.1992.tb14225.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arribas S., Galvan R., Ferrer M., Herguido M. J., Marin J., Balfagón G. Characterization of the subtype of presynaptic alpha 2-adrenoceptors modulating noradrenaline release in cat and bovine cerebral arteries. J Pharm Pharmacol. 1991 Dec;43(12):855–859. doi: 10.1111/j.2042-7158.1991.tb03194.x. [DOI] [PubMed] [Google Scholar]
  3. Blaxall H. S., Murphy T. J., Baker J. C., Ray C., Bylund D. B. Characterization of the alpha-2C adrenergic receptor subtype in the opossum kidney and in the OK cell line. J Pharmacol Exp Ther. 1991 Oct;259(1):323–329. [PubMed] [Google Scholar]
  4. Bylund D. B., Ray-Prenger C. Alpha-2A and alpha-2B adrenergic receptor subtypes: attenuation of cyclic AMP production in cell lines containing only one receptor subtype. J Pharmacol Exp Ther. 1989 Nov;251(2):640–644. [PubMed] [Google Scholar]
  5. Bylund D. B., Ray-Prenger C., Murphy T. J. Alpha-2A and alpha-2B adrenergic receptor subtypes: antagonist binding in tissues and cell lines containing only one subtype. J Pharmacol Exp Ther. 1988 May;245(2):600–607. [PubMed] [Google Scholar]
  6. Bylund D. B. Subtypes of alpha 2-adrenoceptors: pharmacological and molecular biological evidence converge. Trends Pharmacol Sci. 1988 Oct;9(10):356–361. doi: 10.1016/0165-6147(88)90254-4. [DOI] [PubMed] [Google Scholar]
  7. Cheung Y. D., Barnett D. B., Nahorski S. R. Heterogeneous properties of alpha 2 adrenoceptors in particulate and soluble preparations of human platelet and rat and rabbit kidney. Biochem Pharmacol. 1986 Nov 1;35(21):3767–3775. doi: 10.1016/0006-2952(86)90663-5. [DOI] [PubMed] [Google Scholar]
  8. Commarato M. A., Langley A. E., Dugan D. H., Lattime E. C., Smith R. D., Tessman D. K., Kaplan H. R. Prazosin and phentolamine: comparative cardiovascular and autonomic profiles. Clin Exp Hypertens. 1978;1(2):191–217. doi: 10.3109/10641967809068604. [DOI] [PubMed] [Google Scholar]
  9. Connaughton S., Docherty J. R. Functional evidence for heterogeneity of peripheral prejunctional alpha 2-adrenoceptors. Br J Pharmacol. 1990 Oct;101(2):285–290. doi: 10.1111/j.1476-5381.1990.tb12702.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gobbi M., Frittoli E., Mennini T. The modulation of [3H]noradrenaline and [3H]serotonin release from rat brain synaptosomes is not mediated by the alpha 2B-adrenoceptor subtype. Naunyn Schmiedebergs Arch Pharmacol. 1990 Oct;342(4):382–386. doi: 10.1007/BF00169453. [DOI] [PubMed] [Google Scholar]
  11. Harrison J. K., D'Angelo D. D., Zeng D. W., Lynch K. R. Pharmacological characterization of rat alpha 2-adrenergic receptors. Mol Pharmacol. 1991 Sep;40(3):407–412. [PubMed] [Google Scholar]
  12. Lanier S. M., Downing S., Duzic E., Homcy C. J. Isolation of rat genomic clones encoding subtypes of the alpha 2-adrenergic receptor. Identification of a unique receptor subtype. J Biol Chem. 1991 Jun 5;266(16):10470–10478. [PubMed] [Google Scholar]
  13. Limberger N., Mayer A., Zier G., Valenta B., Starke K., Singer E. A. Estimation of pA2 values at presynaptic alpha 2-autoreceptors in rabbit and rat brain cortex in the absence of autoinhibition. Naunyn Schmiedebergs Arch Pharmacol. 1989 Dec;340(6):639–647. doi: 10.1007/BF00717739. [DOI] [PubMed] [Google Scholar]
  14. Limberger N., Späth L., Starke K. Subclassification of the presynaptic alpha 2-autoreceptors in rabbit brain cortex. Br J Pharmacol. 1991 May;103(1):1251–1255. doi: 10.1111/j.1476-5381.1991.tb12332.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Limberger N., Trendelenburg A. U., Starke K. Pharmacological characterization of presynaptic alpha 2-autoreceptors in rat submaxillary gland and heart atrium. Br J Pharmacol. 1992 Sep;107(1):246–255. doi: 10.1111/j.1476-5381.1992.tb14494.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lomasney J. W., Cotecchia S., Lefkowitz R. J., Caron M. G. Molecular biology of alpha-adrenergic receptors: implications for receptor classification and for structure-function relationships. Biochim Biophys Acta. 1991 Oct 26;1095(2):127–139. doi: 10.1016/0167-4889(91)90075-9. [DOI] [PubMed] [Google Scholar]
  17. Michel A. D., Loury D. N., Whiting R. L. Assessment of imiloxan as a selective alpha 2B-adrenoceptor antagonist. Br J Pharmacol. 1990 Mar;99(3):560–564. doi: 10.1111/j.1476-5381.1990.tb12968.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Michel A. D., Loury D. N., Whiting R. L. Differences between the alpha 2-adrenoceptor in rat submaxillary gland and the alpha 2A-and alpha 2B-adrenoceptor subtypes. Br J Pharmacol. 1989 Nov;98(3):890–897. doi: 10.1111/j.1476-5381.1989.tb14618.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nebigil C., Malik K. U. Prostaglandin synthesis elicited by adrenergic stimuli is mediated via alpha-2C and alpha-1A adrenergic receptors in cultured smooth muscle cells of rabbit aorta. J Pharmacol Exp Ther. 1992 Feb;260(2):849–858. [PubMed] [Google Scholar]
  20. Neylon C. B., Summers R. J. [3H]-rauwolscine binding to alpha 2-adrenoceptors in the mammalian kidney: apparent receptor heterogeneity between species. Br J Pharmacol. 1985 Jun;85(2):349–359. doi: 10.1111/j.1476-5381.1985.tb08868.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Regan J. W., Kobilka T. S., Yang-Feng T. L., Caron M. G., Lefkowitz R. J., Kobilka B. K. Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6301–6305. doi: 10.1073/pnas.85.17.6301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rump L. C., Majewski H. Modulation of norepinephrine release through alpha 1- and alpha 2-adrenoceptors in rat isolated kidney. J Cardiovasc Pharmacol. 1987 Apr;9(4):500–507. doi: 10.1097/00005344-198704000-00016. [DOI] [PubMed] [Google Scholar]
  23. Rump L. C., Wilde K., Bohmann C., Schollmeyer P. Effects of the novel dopamine DA2-receptor agonist carmoxirole (EMD 45609) on noradrenergic and purinergic neurotransmission in rat isolated kidney. Naunyn Schmiedebergs Arch Pharmacol. 1992 Mar;345(3):300–308. doi: 10.1007/BF00168691. [DOI] [PubMed] [Google Scholar]
  24. Rump L. C., Wilde K., Schollmeyer P. Prostaglandin E2 inhibits noradrenaline release and purinergic pressor responses to renal nerve stimulation at 1 Hz in isolated kidneys of young spontaneously hypertensive rats. J Hypertens. 1990 Oct;8(10):897–908. doi: 10.1097/00004872-199010000-00003. [DOI] [PubMed] [Google Scholar]
  25. Schmitz J. M., Graham R. M., Sagalowsky A., Pettinger W. A. Renal alpha-1 and alpha-2 adrenergic receptors: biochemical and pharmacological correlations. J Pharmacol Exp Ther. 1981 Nov;219(2):400–406. [PubMed] [Google Scholar]
  26. Schwartz D. D., Malik K. U. Characterization of prejunctional alpha-2 adrenergic receptors involved in modulation of adrenergic transmitter release in the isolated perfused rat kidney. J Pharmacol Exp Ther. 1992 Jun;261(3):1050–1055. [PubMed] [Google Scholar]
  27. Shen K. Z., Barajas-Lopez C., Surprenant A. Functional characterization of neuronal pre and postsynaptic alpha 2-adrenoceptor subtypes in guinea-pig submucosal plexus. Br J Pharmacol. 1990 Dec;101(4):925–931. doi: 10.1111/j.1476-5381.1990.tb14182.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Simonneaux V., Ebadi M., Bylund D. B. Identification and characterization of alpha 2D-adrenergic receptors in bovine pineal gland. Mol Pharmacol. 1991 Aug;40(2):235–241. [PubMed] [Google Scholar]
  29. Singer E. A. Transmitter release from brain slices elicited by single pulses: a powerful method to study presynaptic mechanisms. Trends Pharmacol Sci. 1988 Aug;9(8):274–276. doi: 10.1016/0165-6147(88)90004-1. [DOI] [PubMed] [Google Scholar]
  30. Smith K., Connaughton S., Docherty J. R. Investigations of prejunctional alpha 2-adrenoceptors in rat atrium, vas deferens and submandibular gland. Eur J Pharmacol. 1992 Feb 11;211(2):251–256. doi: 10.1016/0014-2999(92)90536-d. [DOI] [PubMed] [Google Scholar]
  31. Starke K. Presynaptic alpha-autoreceptors. Rev Physiol Biochem Pharmacol. 1987;107:73–146. [PubMed] [Google Scholar]
  32. Starke K. Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol. 1977;77:1–124. doi: 10.1007/BFb0050157. [DOI] [PubMed] [Google Scholar]
  33. Story D. F., McCulloch M. W., Rand M. J., Standford-Starr C. A. Conditions required for the inhibitory feedback loop in noradrenergic transmission. Nature. 1981 Sep 3;293(5827):62–65. doi: 10.1038/293062a0. [DOI] [PubMed] [Google Scholar]
  34. Uhlén S., Wikberg J. E. Delineation of rat kidney alpha 2A- and alpha 2B-adrenoceptors with [3H]RX821002 radioligand binding: computer modelling reveals that guanfacine is an alpha 2A-selective compound. Eur J Pharmacol. 1991 Sep 17;202(2):235–243. doi: 10.1016/0014-2999(91)90299-6. [DOI] [PubMed] [Google Scholar]
  35. Uhlén S., Wikberg J. E. Delineation of three pharmacological subtypes of alpha 2-adrenoceptor in the rat kidney. Br J Pharmacol. 1991 Nov;104(3):657–664. doi: 10.1111/j.1476-5381.1991.tb12485.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Young P., Berge J., Chapman H., Cawthorne M. A. Novel alpha 2-adrenoceptor antagonists show selectivity for alpha 2A- and alpha 2B-adrenoceptor subtypes. Eur J Pharmacol. 1989 Sep 22;168(3):381–386. doi: 10.1016/0014-2999(89)90801-7. [DOI] [PubMed] [Google Scholar]
  37. Zeng D. W., Harrison J. K., D'Angelo D. D., Barber C. M., Tucker A. L., Lu Z. H., Lynch K. R. Molecular characterization of a rat alpha 2B-adrenergic receptor. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3102–3106. doi: 10.1073/pnas.87.8.3102. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES