Evidence for the presence of CB2-like cannabinoid receptors on peripheral nerve terminals.
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.
Griffin
G
G
Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Scotland, UK.
Fernando
S R
SR
Ross
R A
RA
McKay
N G
NG
Ashford
M L
ML
Shire
D
D
Huffman
J W
JW
Yu
S
S
Lainton
J A
JA
Pertwee
R G
RG
D000595:Amino Acid Sequence; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000502:physiology; D009197:Myenteric Plexus / Q000737:chemistry*; D009411:Nerve Endings / Q000737:chemistry*; D010525:Peripheral Nerves / Q000737:chemistry*; D016133:Polymerase Chain Reaction / Q000379:methods; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000032:analysis*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014649:Vas Deferens / Q000187:drug effects
D043882:Receptors, Cannabinoid; D011955:Receptors, Drug