Evidence for the presence of CB2-like cannabinoid receptors on peripheral nerve terminals

G Griffin, S R Fernando, Ruth Alexandra Ross, George McKay, M L J Ashford, D Shire, J W Huffman, S Yu, J A H Lainton, Roger Guy Pertwee

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

We have investigated whether there are cannabinoid CB2 receptors that can mediate cannabinoid-induced inhibition of electrically evoked contractions in the mouse vas deferens or guinea-pig myenteric plexus-longitudinal muscle preparation. Our results showed that mouse vas deferens and guinea-pig whole gut contain cannabinoid CB1 and CB2-like mRNA whereas the myenteric plexus preparation seemed to contain only cannabinoid CB1 mRNA. JWH-015 (1-propyl-2-methyl-3-(1-naphthoyl)indole and JWH-051 (1-deoxy-11-hydroxy-Delta(8)-tetrahydrocannabinol-dimethylheptyl), which have higher affinities for CB2 than CB1 cannabinoid binding sites, inhibited electrically evoked contractions of both tissues in a concentration related manner. This inhibition was attenuated by 31.62 nM of the cannabinoid CB1 receptor selective antagonist SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride] only in the myenteric plexus preparation. Vasa deferentia from Delta(9)-tetrahydrocannabinol-pretreated mice (20 mg/kg i.p. once daily for two days) showed reduced sensitivity to JWH-015 and JWH-051. The results suggest that these compounds exert their inhibitory effects through cannabinoid CB1 receptors in the myenteric plexus preparation, but mainly through CB2-like cannabinoid receptors in the vas deferens. (C) 1997 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)53-61
Number of pages9
JournalEuropean Journal of Pharmacology
Volume339
Issue number1
DOIs
Publication statusPublished - 19 Nov 1997

Keywords

  • cannabinoids
  • Cannabinoid CB1 receptors
  • Cannabinoid CB2 receptors
  • SR141716A
  • vas deferens, mouse
  • myenteric plexus-longitudinal muscle preparation
  • guinea-pig small intestine
  • MOUSE VAS-DEFERENS
  • PIG SMALL-INTESTINE
  • SYMPATHETIC-NERVES
  • GUINEA-PIG
  • ADENOSINE 5'-TRIPHOSPHATE
  • NORADRENALINE
  • ANTAGONIST
  • BINDING
  • CB2
  • PHARMACOLOGY
  • Cannabinoids
  • Vas deferens, mouse
  • Myenteric plexus-longitudinal muscle preparation

Cite this

Evidence for the presence of CB2-like cannabinoid receptors on peripheral nerve terminals. / Griffin, G ; Fernando, S R ; Ross, Ruth Alexandra; McKay, George; Ashford, M L J ; Shire, D ; Huffman, J W ; Yu, S ; Lainton, J A H ; Pertwee, Roger Guy.

In: European Journal of Pharmacology, Vol. 339, No. 1, 19.11.1997, p. 53-61.

Research output: Contribution to journalArticle

Griffin, G, Fernando, SR, Ross, RA, McKay, G, Ashford, MLJ, Shire, D, Huffman, JW, Yu, S, Lainton, JAH & Pertwee, RG 1997, 'Evidence for the presence of CB2-like cannabinoid receptors on peripheral nerve terminals', European Journal of Pharmacology, vol. 339, no. 1, pp. 53-61. https://doi.org/10.1016/S0014-2999(97)01336-8
Griffin, G ; Fernando, S R ; Ross, Ruth Alexandra ; McKay, George ; Ashford, M L J ; Shire, D ; Huffman, J W ; Yu, S ; Lainton, J A H ; Pertwee, Roger Guy. / Evidence for the presence of CB2-like cannabinoid receptors on peripheral nerve terminals. In: European Journal of Pharmacology. 1997 ; Vol. 339, No. 1. pp. 53-61.
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AB - We have investigated whether there are cannabinoid CB2 receptors that can mediate cannabinoid-induced inhibition of electrically evoked contractions in the mouse vas deferens or guinea-pig myenteric plexus-longitudinal muscle preparation. Our results showed that mouse vas deferens and guinea-pig whole gut contain cannabinoid CB1 and CB2-like mRNA whereas the myenteric plexus preparation seemed to contain only cannabinoid CB1 mRNA. JWH-015 (1-propyl-2-methyl-3-(1-naphthoyl)indole and JWH-051 (1-deoxy-11-hydroxy-Delta(8)-tetrahydrocannabinol-dimethylheptyl), which have higher affinities for CB2 than CB1 cannabinoid binding sites, inhibited electrically evoked contractions of both tissues in a concentration related manner. This inhibition was attenuated by 31.62 nM of the cannabinoid CB1 receptor selective antagonist SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride] only in the myenteric plexus preparation. Vasa deferentia from Delta(9)-tetrahydrocannabinol-pretreated mice (20 mg/kg i.p. once daily for two days) showed reduced sensitivity to JWH-015 and JWH-051. The results suggest that these compounds exert their inhibitory effects through cannabinoid CB1 receptors in the myenteric plexus preparation, but mainly through CB2-like cannabinoid receptors in the vas deferens. (C) 1997 Elsevier Science B.V.

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