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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Apr;105(4):980–984. doi: 10.1111/j.1476-5381.1992.tb09088.x

Inhibitory effects of certain enantiomeric cannabinoids in the mouse vas deferens and the myenteric plexus preparation of guinea-pig small intestine.

R G Pertwee 1, L A Stevenson 1, D B Elrick 1, R Mechoulam 1, A D Corbett 1
PMCID: PMC1908724  PMID: 1324060

Abstract

1. The psychoactive cannabinoids (-)-delta 9-tetrahydrocannabinol ((-)-delta 9-THC) and the 1,1-dimethyl-heptyl homologue of (-)-11-hydroxy-delta 8-tetrahydrocannabinol ((-)-DMH) both inhibited electrically-evoked contractions of the mouse isolated vas deferens and the myenteric plexus-longitudinal muscle preparation of the guinea-pig small intestine. 2. Concentrations of (-)-delta 9-THC and (-)-DMH that decreased twitch heights by 50% were 6.3 and 0.15 nM respectively in the mouse vas deferens and 60 nM and 1.4 nM respectively in the myenteric plexus preparation. (-)-DMH was about 40 times more potent than (-)-delta 9-THC in both preparations, supporting the notion that their mode of action in each tissue is the same. 3. The psychically inactive cannabinoid, (+)-DMH, had no inhibitory effect in the mouse vas deferens at a concentration of 30 nM, showing it to be at least 1000 times less potent than (-)-DMH. In the myenteric plexus preparation, (+)-DMH was about 500 times less potent than its (-)-enantiomer. 4. The inhibitory effects of sub-maximal concentrations of (-)-delta 9-THC were not attenuated by 300 nM naloxone. 5. The findings that (-)-delta 9-THC and (-)-DMH are highly potent as inhibitors of the twitch response of the mouse vas deferens and guinea-pig myenteric plexus preparation and that DMH shows considerable stereoselectivity suggest that the inhibitory effects of cannabinoids in these preparations are mediated by cannabinoid receptors.

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Selected References

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  1. Anderson P. F., Jackson D. M., Chesher G. B., Malor R. Tolerance to the effect of delta9-tetrahydrocannabinol in mice on intestinal motility, temperature and locomotor activity. Psychopharmacologia. 1975 Jul 23;43(1):31–36. doi: 10.1007/BF00437611. [DOI] [PubMed] [Google Scholar]
  2. Bidaut-Russell M., Devane W. A., Howlett A. C. Cannabinoid receptors and modulation of cyclic AMP accumulation in the rat brain. J Neurochem. 1990 Jul;55(1):21–26. doi: 10.1111/j.1471-4159.1990.tb08815.x. [DOI] [PubMed] [Google Scholar]
  3. Corbett A. D., Gillan M. G., Kosterlitz H. W., McKnight A. T., Paterson S. J., Robson L. E. Selectivities of opioid peptide analogues as agonists and antagonists at the delta-receptor. Br J Pharmacol. 1984 Sep;83(1):271–279. doi: 10.1111/j.1476-5381.1984.tb10143.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Devane W. A., Dysarz F. A., 3rd, Johnson M. R., Melvin L. S., Howlett A. C. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol. 1988 Nov;34(5):605–613. [PubMed] [Google Scholar]
  5. Herkenham M., Lynn A. B., Johnson M. R., Melvin L. S., de Costa B. R., Rice K. C. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci. 1991 Feb;11(2):563–583. doi: 10.1523/JNEUROSCI.11-02-00563.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Herkenham M., Lynn A. B., Little M. D., Johnson M. R., Melvin L. S., de Costa B. R., Rice K. C. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1932–1936. doi: 10.1073/pnas.87.5.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hillard C. J., Pounds J. J., Boyer D. R., Bloom A. S. Studies of the role of membrane lipid order in the effects of delta 9-tetrahydrocannabinol on adenylate cyclase activation in heart. J Pharmacol Exp Ther. 1990 Mar;252(3):1075–1082. [PubMed] [Google Scholar]
  8. Hughes J., Kosterlitz H. W., Leslie F. M. Effect of morphine on adrenergic transmission in the mouse vas deferens. Assessment of agonist and antogonist potencies of narcotic analgesics. Br J Pharmacol. 1975 Mar;53(3):371–381. doi: 10.1111/j.1476-5381.1975.tb07373.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Järbe T. U., Hiltunen A. J., Mechoulam R. Stereospecificity of the discriminative stimulus functions of the dimethylheptyl homologs of 11-hydroxy-delta 8-tetrahydrocannabinol in rats and pigeons. J Pharmacol Exp Ther. 1989 Sep;250(3):1000–1005. [PubMed] [Google Scholar]
  10. Kosterlitz H. W., Lydon R. J., Watt A. J. The effects of adrenaline, noradrenaline and isoprenaline on inhibitory alpha- and beta-adrenoceptors in the longitudinal muscle of the guinea-pig ileum. Br J Pharmacol. 1970 Jun;39(2):398–413. doi: 10.1111/j.1476-5381.1970.tb12903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Leslie F. M. Methods used for the study of opioid receptors. Pharmacol Rev. 1987 Sep;39(3):197–249. [PubMed] [Google Scholar]
  12. Little P. J., Compton D. R., Mechoulam R., Martin B. R. Stereochemical effects of 11-OH-delta 8-THC-dimethylheptyl in mice and dogs. Pharmacol Biochem Behav. 1989 Mar;32(3):661–666. doi: 10.1016/0091-3057(89)90014-2. [DOI] [PubMed] [Google Scholar]
  13. Matsuda L. A., Lolait S. J., Brownstein M. J., Young A. C., Bonner T. I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990 Aug 9;346(6284):561–564. doi: 10.1038/346561a0. [DOI] [PubMed] [Google Scholar]
  14. Pacheco M., Childers S. R., Arnold R., Casiano F., Ward S. J. Aminoalkylindoles: actions on specific G-protein-linked receptors. J Pharmacol Exp Ther. 1991 Apr;257(1):170–183. [PubMed] [Google Scholar]
  15. Paton W. D., Zar M. A. The origin of acetylcholine released from guinea-pig intestine and longitudinal muscle strips. J Physiol. 1968 Jan;194(1):13–33. doi: 10.1113/jphysiol.1968.sp008392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pertwee R. G., Wickens A. P. Enhancement by chlordiazepoxide of catalepsy induced in rats by intravenous or intrapallidal injections of enantiomeric cannabinoids. Neuropharmacology. 1991 Mar;30(3):237–244. doi: 10.1016/0028-3908(91)90150-a. [DOI] [PubMed] [Google Scholar]
  17. Roth S. H. Stereospecific presynaptic inhibitory effect of delta9-tetrahydrocannabinol on cholinergic transmission in the myenteric plexus of the guinea pig. Can J Physiol Pharmacol. 1978 Dec;56(6):968–975. doi: 10.1139/y78-154. [DOI] [PubMed] [Google Scholar]
  18. Roth S. H., Williams P. J. The non-specific membrane binding properties of delta9-tetrahydrocannabinol and the effects of various solubilizers. J Pharm Pharmacol. 1979 Apr;31(4):224–230. doi: 10.1111/j.2042-7158.1979.tb13484.x. [DOI] [PubMed] [Google Scholar]
  19. Thomas B. F., Compton D. R., Martin B. R. Characterization of the lipophilicity of natural and synthetic analogs of delta 9-tetrahydrocannabinol and its relationship to pharmacological potency. J Pharmacol Exp Ther. 1990 Nov;255(2):624–630. [PubMed] [Google Scholar]

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