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. 1988 Sep;95(1):33–38. doi: 10.1111/j.1476-5381.1988.tb16545.x

Alfaxalone potentiates and mimics GABA-induced contractile responses in the guinea-pig isolated ileum.

J Ong 1, D I Kerr 1, G A Johnston 1
PMCID: PMC1854129  PMID: 3219474

Abstract

1. Alfaxalone (1-100 nM) potentiated gamma-aminobutyric acidA (GABAA)-receptor-mediated contractile responses in the guinea-pig isolated ileum, with a leftward shift of the GABA concentration-response curve, and a significant potentiation of the GABA-induced contractions over the lower concentration-range for GABA (3-30 microM). Alfadalone on the other hand, did not affect contractile responses to GABA. 2. Picrotoxinin (10 microM) induced a non-parallel rightward shift of the GABA concentration-response curve, with a 50% depression of the maximum response to GABA. Alfaxalone (100 nM) potentiated the responses to GABA in the presence of picrotoxinin (10 microM) over the GABA concentration-range of 10-100 microM, causing a leftward shift of the concentration-response curve, but without affecting the depression of the maximum response by picrotoxinin. 3. Bicuculline methochloride (10 microM) caused a parallel rightward shift of the GABA concentration-response-curve; the ratio of this shift was unchanged in the presence of alfaxalone (100 microM), although the latter itself displaced the curve leftwards. 4. Alfaxalone (1-100 mM) also induced a similar potentiation of contractile responses to 3-amino-1-propanesulphonic acid (3-APS), a GABA agonist not subject to uptake. Such concentrations of alfaxalone were ineffective against contractile responses to exogenous acetylcholine. 5. Higher concentrations of alfaxalone (1 microM and above), however, elicited a GABA-like ileal contraction, sensitive to both picrotoxinin (10 microM) and bicuculline (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Barker J. L., Harrison N. L., Lange G. D., Owen D. G. Potentiation of gamma-aminobutyric-acid-activated chloride conductance by a steroid anaesthetic in cultured rat spinal neurones. J Physiol. 1987 May;386:485–501. doi: 10.1113/jphysiol.1987.sp016547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cottrell G. A., Lambert J. J., Peters J. A. Modulation of GABAA receptor activity by alphaxalone. Br J Pharmacol. 1987 Mar;90(3):491–500. doi: 10.1111/j.1476-5381.1987.tb11198.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gee K. W., Chang W. C., Brinton R. E., McEwen B. S. GABA-dependent modulation of the Cl- ionophore by steroids in rat brain. Eur J Pharmacol. 1987 Apr 29;136(3):419–423. doi: 10.1016/0014-2999(87)90317-7. [DOI] [PubMed] [Google Scholar]
  4. Gyermek L., Soyka L. F. Steroid anesthetics. Anesthesiology. 1975 Mar;42(3):331–344. doi: 10.1097/00000542-197503000-00017. [DOI] [PubMed] [Google Scholar]
  5. HEUSER G., EIDELBERG E. Steroid-induced convulsions in experimental animals. Endocrinology. 1961 Nov;69:915–924. doi: 10.1210/endo-69-5-915. [DOI] [PubMed] [Google Scholar]
  6. Harrison N. L., Majewska M. D., Harrington J. W., Barker J. L. Structure-activity relationships for steroid interaction with the gamma-aminobutyric acidA receptor complex. J Pharmacol Exp Ther. 1987 Apr;241(1):346–353. [PubMed] [Google Scholar]
  7. Harrison N. L., Simmonds M. A. Modulation of the GABA receptor complex by a steroid anaesthetic. Brain Res. 1984 Dec 10;323(2):287–292. doi: 10.1016/0006-8993(84)90299-3. [DOI] [PubMed] [Google Scholar]
  8. Harrison N. L., Simmonds M. A. Two distinct interactions of barbiturates and chlormethiazole with the GABAA receptor complex in rat cuneate nucleus in vitro. Br J Pharmacol. 1983 Oct;80(2):387–394. doi: 10.1111/j.1476-5381.1983.tb10045.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Harrison N. L., Vicini S., Barker J. L. A steroid anesthetic prolongs inhibitory postsynaptic currents in cultured rat hippocampal neurons. J Neurosci. 1987 Feb;7(2):604–609. doi: 10.1523/JNEUROSCI.07-02-00604.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kerr D. I., Ong J., Prager R. H., Ward D. A. Caprolactam-barbiturate interaction at the GABAA receptor complex in the guinea-pig intestine. Eur J Pharmacol. 1986 May 13;124(1-2):203–206. doi: 10.1016/0014-2999(86)90146-9. [DOI] [PubMed] [Google Scholar]
  11. Lodge D., Anis N. A. Effects of ketamine and three other anaesthetics on spinal reflexes and inhibitions in the cat. Br J Anaesth. 1984 Oct;56(10):1143–1151. doi: 10.1093/bja/56.10.1143. [DOI] [PubMed] [Google Scholar]
  12. Majewska M. D., Harrison N. L., Schwartz R. D., Barker J. L., Paul S. M. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science. 1986 May 23;232(4753):1004–1007. doi: 10.1126/science.2422758. [DOI] [PubMed] [Google Scholar]
  13. Ong J., Kerr D. I., Johnston G. A. Cortisol: a potent biphasic modulator at GABAA-receptor complexes in the guinea pig isolated ileum. Neurosci Lett. 1987 Nov 10;82(1):101–106. doi: 10.1016/0304-3940(87)90178-9. [DOI] [PubMed] [Google Scholar]
  14. Ong J., Kerr D. I. Potentiation of GABAA-receptor-mediated responses by barbiturates in the guinea-pig ileum. Eur J Pharmacol. 1984 Aug 17;103(3-4):327–332. doi: 10.1016/0014-2999(84)90494-1. [DOI] [PubMed] [Google Scholar]
  15. Ong J. Uptake inhibitors potentiate gamma-aminobutyric acid-induced contractile responses in the isolated ileum of the guinea-pig. Br J Pharmacol. 1987 May;91(1):9–15. doi: 10.1111/j.1476-5381.1987.tb08977.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Scholfield C. N. Potentiation of inhibition by general anaesthetics in neurones of the olfactory cortex in vitro. Pflugers Arch. 1980 Feb;383(3):249–255. doi: 10.1007/BF00587527. [DOI] [PubMed] [Google Scholar]
  17. Schulz D. W., Macdonald R. L. Barbiturate enhancement of GABA-mediated inhibition and activation of chloride ion conductance: correlation with anticonvulsant and anesthetic actions. Brain Res. 1981 Mar 23;209(1):177–188. doi: 10.1016/0006-8993(81)91179-3. [DOI] [PubMed] [Google Scholar]
  18. Sear J. W., Prys-Roberts C. Plasma concentrations of alphaxalone during continuous infusion of Althesin. Br J Anaesth. 1979 Sep;51(9):861–865. doi: 10.1093/bja/51.9.861. [DOI] [PubMed] [Google Scholar]

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