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

Graeme Griffin, Susanthu R. Fernando, Ruth A. Ross, Neil G. McKay, M L Ashford, David Shire, John W. Huffman, Shu Yu, Julia A. H. Lainton, Roger G Pertwee

    Research output: Contribution to journalArticlepeer-review

    158 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-( -naphthoyl)indole) and JWH-051 (1-deoxy-11-hydroxy-delta8-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-me thyl-1H-pyrazole-3-carboxamide hydrochloride] only in the myenteric plexus preparation. Vasa deferentia from delta9-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.
    Original languageEnglish
    Pages (from-to)53-61
    Number of pages9
    JournalEuropean Journal of Pharmacology
    Volume339
    Issue number1
    DOIs
    Publication statusPublished - 19 Nov 1997

    Keywords

    • Vas Deferens
    • Animals
    • Guinea Pigs
    • Humans
    • Transcription, Genetic
    • Amino Acid Sequence
    • Mice
    • Electric Stimulation
    • Receptors, Cannabinoid
    • Myenteric Plexus
    • Peripheral Nerves
    • Polymerase Chain Reaction
    • Receptors, Drug
    • Intestine, Small
    • Molecular Sequence Data
    • Nerve Endings
    • Muscle Contraction
    • Sequence Homology, Amino Acid
    • Male

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