Cannabinoid receptor type 1 modulates excitatory and inhibitory neurotransmission in mouse colon.
American Journal of Physiology-Gastrointestinal and Liver Physiology. 2004-01-01; 286(1): G110-G117
DOI: 10.1152/ajpgi.00148.2003
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1. Am J Physiol Gastrointest Liver Physiol. 2004 Jan;286(1):G110-7. Epub 2003 Jul
31.
Cannabinoid receptor type 1 modulates excitatory and inhibitory neurotransmission
in mouse colon.
Storr M(1), Sibaev A, Marsicano G, Lutz B, Schusdziarra V, Timmermans JP,
Allescher HD.
Author information:
(1)GAP, Department of Internal Medicine II, Technical University of Munich, 81675
Munich, Germany.
The effects of cannabinoid receptor agonists and antagonists on smooth muscle
resting membrane potentials and on membrane potentials following electrical
neuronal stimulation in a myenteric neuron/smooth muscle preparation of wild-type
and cannabinoid receptor type 1 (CB1)-deficient mice were investigated in vitro.
Double staining for CB1 and nitric oxide synthase (neuronal) was performed to
identify the myenteric CB1-expressing neurons. Focal electrical stimulation of
the myenteric plexus induced a fast (f) excitatory junction potential (EJP)
followed by a fast and a slow (s) inhibitory junction potential (IJP). Treatment
of wild-type mice with the endogenous CB1 receptor agonist anandamide reduced EJP
while not affecting fIJP and sIJP. EJP was significantly higher in CB1-deficient
mice than in wild-type littermate controls, and anandamide induced no effects in
CB1-deficient mice. N-arachidonoyl ethanolamide (anandamide),
R-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3,-de]-
1,4-benzoxazin-6-yl]-1-naphtalenylmethanone, a synthetic CB1 receptor agonist,
nearly abolished EJP and significantly reduced the fIJP in wild-type mice.
N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-caroxa
mide (SR141716A), a CB1-specific receptor antagonist, was able to reverse the
agonist effects induced in wild-type mice. SR141716A, when given alone,
significantly increased EJP in wild-type mice without affecting IJP in wild-type
and EJP in CB1-deficient mice. Interestingly, SR141716A reduced fIJP in
CB1-deficient mice. In the mouse colon, nitrergic myenteric neurons do not
express CB1, implying that CB1 is expressed in cholinergic neurons, which is in
line with the functional data. Finally, excitatory and inhibitory
neurotransmission in the mouse colon is modulated by activation of CB1 receptors.
The significant increase in EJP in CB1-deficient mice strongly suggests a
physiological involvement of CB1 in excitatory cholinergic neurotransmission.
DOI: 10.1152/ajpgi.00148.2003
PMID: 12893627 [Indexed for MEDLINE]