Evidence that methyl arachidonyl fluorophosphonate is an irreversible cannabinoid receptor antagonist

S R Fernando, Roger Guy Pertwee

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

1 Methyl arachidonyl fluorophosphonate (MAFP) (1 mu M) significantly attenuated the ability of WIN 55,212-2, CP 55,940, (-)-Delta(9)-tetrahydrocannabinol (THC), nabilone and (R)-(+)-arachidonoyl-1'-hydroxy-2'-propylamide (methanandamide) to inhibit electrically-evoked isometric contractions of the myenteric plexus-longitudinal muscle preparation of guinea-pig small intestine,

2 The sizes of the maximal responses to WIN 55,212-2 and CP 55,940 decreased significantly in the presence of 1 mu M MAFP.

3 MAFP (1 mu M) essentially abolished the inhibitory effects on the twitch response of the highest concentration of methanandamide used (3.162 mu M). The dextral shift it induced in the log concentration-response curve of nabilone was non-parallel. In contrast, the dextral shift in the log concentration-response curve of THC produced by MAFP did not deviate significantly from parallelism and was relatively small with a mean value of 3.45 and 95% confidence limits of 1.19 and 13.08.

4 MAFP (1 mu M) did not attenuate the effects of normorphine or clonidine on the twitch response of the myenteric plexus-longitudinal muscle preparation or affect the contractile response of this preparation to acetylcholine.

5 When administered by itself at concentrations of I to 1000 nM, MAFP had no detectable effect on the twitch response of the myenteric plexus-longitudinal muscle preparation.

6 These results support the hypothesis that MAFP is an irreversible cannabinoid CB1 receptor antagonist that possesses some degree of selectivity.

Original languageEnglish
Pages (from-to)1716-1720
Number of pages5
JournalBritish Journal of Pharmacology
Volume121
Issue number8
DOIs
Publication statusPublished - Aug 1997

Keywords

  • methyl arachidonyl fluorophosphonate
  • myenteric plexus
  • guinea-pig small intestine
  • cannabinoid receptor agonists
  • cannabinoid receptor antagonist
  • Delta(9)-tetrahydrocannabinol
  • GUINEA-PIG
  • MYENTERIC PLEXUS
  • ANANDAMIDE
  • POTENCY
  • Methyl arachidonyl fluorophosphonate
  • myenteric plexus
  • guinea-pig small intestine
  • cannabinoid receptor agonists
  • cannabinoid receptor antagonist
  • tetrahydrocannabinol

Cite this

Evidence that methyl arachidonyl fluorophosphonate is an irreversible cannabinoid receptor antagonist. / Fernando, S R ; Pertwee, Roger Guy.

In: British Journal of Pharmacology, Vol. 121, No. 8, 08.1997, p. 1716-1720.

Research output: Contribution to journalArticle

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abstract = "1 Methyl arachidonyl fluorophosphonate (MAFP) (1 mu M) significantly attenuated the ability of WIN 55,212-2, CP 55,940, (-)-Delta(9)-tetrahydrocannabinol (THC), nabilone and (R)-(+)-arachidonoyl-1'-hydroxy-2'-propylamide (methanandamide) to inhibit electrically-evoked isometric contractions of the myenteric plexus-longitudinal muscle preparation of guinea-pig small intestine,2 The sizes of the maximal responses to WIN 55,212-2 and CP 55,940 decreased significantly in the presence of 1 mu M MAFP.3 MAFP (1 mu M) essentially abolished the inhibitory effects on the twitch response of the highest concentration of methanandamide used (3.162 mu M). The dextral shift it induced in the log concentration-response curve of nabilone was non-parallel. In contrast, the dextral shift in the log concentration-response curve of THC produced by MAFP did not deviate significantly from parallelism and was relatively small with a mean value of 3.45 and 95{\%} confidence limits of 1.19 and 13.08.4 MAFP (1 mu M) did not attenuate the effects of normorphine or clonidine on the twitch response of the myenteric plexus-longitudinal muscle preparation or affect the contractile response of this preparation to acetylcholine.5 When administered by itself at concentrations of I to 1000 nM, MAFP had no detectable effect on the twitch response of the myenteric plexus-longitudinal muscle preparation.6 These results support the hypothesis that MAFP is an irreversible cannabinoid CB1 receptor antagonist that possesses some degree of selectivity.",
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N2 - 1 Methyl arachidonyl fluorophosphonate (MAFP) (1 mu M) significantly attenuated the ability of WIN 55,212-2, CP 55,940, (-)-Delta(9)-tetrahydrocannabinol (THC), nabilone and (R)-(+)-arachidonoyl-1'-hydroxy-2'-propylamide (methanandamide) to inhibit electrically-evoked isometric contractions of the myenteric plexus-longitudinal muscle preparation of guinea-pig small intestine,2 The sizes of the maximal responses to WIN 55,212-2 and CP 55,940 decreased significantly in the presence of 1 mu M MAFP.3 MAFP (1 mu M) essentially abolished the inhibitory effects on the twitch response of the highest concentration of methanandamide used (3.162 mu M). The dextral shift it induced in the log concentration-response curve of nabilone was non-parallel. In contrast, the dextral shift in the log concentration-response curve of THC produced by MAFP did not deviate significantly from parallelism and was relatively small with a mean value of 3.45 and 95% confidence limits of 1.19 and 13.08.4 MAFP (1 mu M) did not attenuate the effects of normorphine or clonidine on the twitch response of the myenteric plexus-longitudinal muscle preparation or affect the contractile response of this preparation to acetylcholine.5 When administered by itself at concentrations of I to 1000 nM, MAFP had no detectable effect on the twitch response of the myenteric plexus-longitudinal muscle preparation.6 These results support the hypothesis that MAFP is an irreversible cannabinoid CB1 receptor antagonist that possesses some degree of selectivity.

AB - 1 Methyl arachidonyl fluorophosphonate (MAFP) (1 mu M) significantly attenuated the ability of WIN 55,212-2, CP 55,940, (-)-Delta(9)-tetrahydrocannabinol (THC), nabilone and (R)-(+)-arachidonoyl-1'-hydroxy-2'-propylamide (methanandamide) to inhibit electrically-evoked isometric contractions of the myenteric plexus-longitudinal muscle preparation of guinea-pig small intestine,2 The sizes of the maximal responses to WIN 55,212-2 and CP 55,940 decreased significantly in the presence of 1 mu M MAFP.3 MAFP (1 mu M) essentially abolished the inhibitory effects on the twitch response of the highest concentration of methanandamide used (3.162 mu M). The dextral shift it induced in the log concentration-response curve of nabilone was non-parallel. In contrast, the dextral shift in the log concentration-response curve of THC produced by MAFP did not deviate significantly from parallelism and was relatively small with a mean value of 3.45 and 95% confidence limits of 1.19 and 13.08.4 MAFP (1 mu M) did not attenuate the effects of normorphine or clonidine on the twitch response of the myenteric plexus-longitudinal muscle preparation or affect the contractile response of this preparation to acetylcholine.5 When administered by itself at concentrations of I to 1000 nM, MAFP had no detectable effect on the twitch response of the myenteric plexus-longitudinal muscle preparation.6 These results support the hypothesis that MAFP is an irreversible cannabinoid CB1 receptor antagonist that possesses some degree of selectivity.

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KW - Methyl arachidonyl fluorophosphonate

KW - myenteric plexus

KW - guinea-pig small intestine

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KW - cannabinoid receptor antagonist

KW - tetrahydrocannabinol

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DO - 10.1038/sj.bjp.0701303

M3 - Article

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SP - 1716

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JO - British Journal of Pharmacology

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SN - 0007-1188

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