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Inhibition of exocytotic noradrenaline release by presynaptic cannabinoid CB 1 receptors on peripheral sympathetic nerves
Author(s) -
Ishac Edward J.N.,
Jiang Liu,
Lake Kristy D.,
Varga Karoly,
Abood Mary E.,
Kunos George
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15639.x
Subject(s) - anandamide , medicine , endocrinology , cannabinoid receptor , capsazepine , cannabinoid , vas deferens , chemistry , receptor , tetrodotoxin , agonist , endocannabinoid system , biology , trpv1 , transient receptor potential channel
1 Activation of CB 1 receptors by plant cannabinoids or the endogenous ligand, anandamide, causes hypotension via a sympathoinhibitory action in anaesthetized rats. In mouse isolated vas deferens, activation of CB 1 receptors inhibits the electrically evoked twitch response. To determine if these effects are related to presynaptic inhibition of noradrenaline (NA) release, we examined the effects of Δ 9 ‐tetrahydrocannabinol (‡ 9 ‐THC), anandamide and the CB 1 antagonist, SR141716A, on exocytotic NA release in rat isolated atria and vasa deferentia. 2 In isolated atria and vasa deferentia preloaded with [ 3 H]‐NA, electrical field stimulation caused [ 3 H]‐NA release, which was abolished by tetrodotoxin 0.5 μ m and concentration‐dependently inhibited by ‡ 9 ‐THC or anandamide, 0.3–10 μ m . The inhibitory effect of ‡ 9 ‐THC and anandamide was competitively antagonized by SR141716A, 1–10 μ m . 3 Tyramine, 1 μ m , also induced [ 3 H]‐NA release, which was unaffected by tetrodotoxin, ‡ 9 ‐THC or anandamide in either atria or vasa deferentia. 4 CB 1 receptor mRNA is present in the superior cervical ganglion, as well as in whole brain, cerebellum, hypothalamus, spleen, and vas deferens and absent in medulla oblongata and atria, as demonstrated by reverse transcription‐polymerase chain reaction. There was no evidence of the presence of CB 1A receptor mRNA in ganglia, brain, or cerebellum. These results suggest that activation of presynaptic CB 1 receptors located on peripheral sympathetic nerve terminals mediate sympathoinhibitory effects in vitro and in vivo.