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

Roger Guy Pertwee, Lesley Ann Stevenson, D B Elrick, R Mechoulam, A D Corbett

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

1 The psychoactive cannabinoids (-)-DELTA(9)-tetrahydrocannabinol ((-)-DELTA(9)-THC) and the 1,1-dimethylheptyl 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 1.4nM 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.

Original languageEnglish
Pages (from-to)980-984
Number of pages5
JournalBritish Journal of Pharmacology
Volume105
Issue number4
Publication statusPublished - Apr 1992

Keywords

  • DELTA-9-TETRAHYDROCANNABINOL
  • CANNABINOIDS
  • MOUSE VAS DEFERENS
  • MYENTERIC PLEXUS
  • GUINEA-PIG SMALL INTESTINE
  • STEREOSELECTIVITY
  • OPIOID RECEPTORS
  • RAT-BRAIN
  • ANALOGS
  • delta-9-tetrahydrocannabinol
  • cannabinoids
  • mouse
  • vas deferens
  • myeneteric plexus
  • guinea-pig small intestine
  • stereoselectivity

Cite this

Inhibitory effects of certain enantiomeric cannabinoids in the mouse vas-deferens and the myenteric plexus preparation of guinea-pig small-intestine. / Pertwee, Roger Guy; Stevenson, Lesley Ann; Elrick, D B ; Mechoulam, R ; Corbett, A D .

In: British Journal of Pharmacology, Vol. 105, No. 4, 04.1992, p. 980-984.

Research output: Contribution to journalArticle

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abstract = "1 The psychoactive cannabinoids (-)-DELTA(9)-tetrahydrocannabinol ((-)-DELTA(9)-THC) and the 1,1-dimethylheptyl 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 1.4nM 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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T1 - Inhibitory effects of certain enantiomeric cannabinoids in the mouse vas-deferens and the myenteric plexus preparation of guinea-pig small-intestine

AU - Pertwee, Roger Guy

AU - Stevenson, Lesley Ann

AU - Elrick, D B

AU - Mechoulam, R

AU - Corbett, A D

PY - 1992/4

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N2 - 1 The psychoactive cannabinoids (-)-DELTA(9)-tetrahydrocannabinol ((-)-DELTA(9)-THC) and the 1,1-dimethylheptyl 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 1.4nM 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.

AB - 1 The psychoactive cannabinoids (-)-DELTA(9)-tetrahydrocannabinol ((-)-DELTA(9)-THC) and the 1,1-dimethylheptyl 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 1.4nM 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.

KW - DELTA-9-TETRAHYDROCANNABINOL

KW - CANNABINOIDS

KW - MOUSE VAS DEFERENS

KW - MYENTERIC PLEXUS

KW - GUINEA-PIG SMALL INTESTINE

KW - STEREOSELECTIVITY

KW - OPIOID RECEPTORS

KW - RAT-BRAIN

KW - ANALOGS

KW - delta-9-tetrahydrocannabinol

KW - cannabinoids

KW - mouse

KW - vas deferens

KW - myeneteric plexus

KW - guinea-pig small intestine

KW - stereoselectivity

M3 - Article

VL - 105

SP - 980

EP - 984

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 4

ER -