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Neural
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The
endogenous cannabinoid anandamide
has a brief pressor effect and a more prolonged
depressor response in anaesthetised rats. The
depressor response is attenuated after transection of
the cervical spinal cord or blockade of alpha adrenergic receptors by phentolamine, and is dose dependently inhibited by a
selective antagonist of the CB1 cannabinoid receptor,
suggesting that it is due to inhibition of sympathetic tone mediated by CB1 receptors. Varga K;
Activation
of CB1 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 CB1 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
delta 9 tetrahydrocannabinol (delta 9 THC), anandamide and the CB1 antagonist, SR141716A, on exocytotic NA release in rat isolated atria and vasa deferentia. 2. In isolated atria and vasa deferentia preloaded with
[3H] NA, electrical field stimulation caused [3H] NA release, which was
abolished by tetrodotoxin 0.5 microM
and concentration dependently inhibited by delta 9 THC or anandamide,
0.3 10 microM. The inhibitory effect of delta 9 THC
and anandamide was competitively antagonized by SR
141716A, 1 10 microM. 3. Tyramine,
1 microM, also induced [3H] NA release, which was
unaffected by tetrodotoxin, delta 9 THC or anandamide in either atria or vasa
deferentia. 4. CB1 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 CB1A receptor
mRNA in ganglia, brain, or cerebellum. These results suggest that activation of
presynaptic CB1 receptors located on peripheral
sympathetic nerve terminals mediate sympathoinhibitory
effects in vitro and in vivo. Ishac EJ; Jiang
L; Lake KD; Varga K; Abood
ME; Kunos G. Inhibition
of exocytotic noradrenaline
release by presynaptic cannabinoid
CB1 receptors on peripheral sympathetic nerves. Br J Pharmacol 1996 Aug;118(8):2023 8.