Interaction between cannabinoid CB(1) receptors and endogenous ATP in the control of spontaneous mechanical activity in mouse ileum

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Abstract

Background and purpose: Although it is well accepted that cannabinoids modulate intestinal motility by reducing cholinergic neurotransmission mediated by CB1 receptors, it is not known whether the endocannabinoids are involved in more complex circuits and if they interact with other systems. The aim of the present study was to examine possible interactions between cannabinoid CB1 receptors and purines in the control of spontaneous contractility of longitudinal muscle in mouse ileum.Experimental approach: The mechanical activity of longitudinally oriented ileal segments from mice was recorded as isometric contractions.Key results: The selective CB1 receptor agonist, N-(2-chloroethyl)5,8,11,14-eicosaetraenamide (ACEA) reduced, concentration dependently, spontaneous contractions in mouse ileum. This effect was almost abolished by tetrodotoxin (TTX) or atropine. Inhibition by ACEA was not affected by theophylline (P1 receptor antagonist) or by P2Y receptor desensitization with adenosine5′[b-thio]diphosphate trilithium salt, but was significantly reversed by pyridoxal phosphate-6-azo(benzene-2,4-disulphonic acid) (P2 receptor antagonist), by P2X receptor desensitization with a,b-methyleneadenosine 5′-triphosphate lithiumsalt (a,b-MeATP) or by 8,8′-[carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino) bis(1,3,5-naphthalenetrisulphonic acid)] (P2X receptor antagonist). Contractile responses to a,b-MeATP (P2X receptor agonist) were virtually abolished by TTX or atropine, suggesting that they were mediated by acetylcholine released from neurones, and significantly reduced by ACEA.Conclusion and implications: In mouse ileum, activation of CB1 receptors, apart from reducing acetylcholine release from cholinergic nerves, was able to modulate negatively, endogenous purinergic effects, mediated by P2X receptors, on cholinergic neurons. Our study provides evidence for a role of cannabinoids in the modulation of interneuronal purinergic transmission.
Lingua originaleEnglish
pagine (da-a)243-251
Numero di pagine9
RivistaBritish Journal of Pharmacology
Volume158
Stato di pubblicazionePublished - 2009

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Purinergic P2 Receptors
Cannabinoid Receptor CB1
Cannabinoids
Ileum
Tetrodotoxin
Atropine
Purinergic Agents
Cholinergic Agents
Acetylcholine
Endocannabinoids
Purines
Cholinergic Neurons
Isometric Contraction
Pyridoxal Phosphate
Gastrointestinal Motility
Acids
Diphosphates
Theophylline
Benzene
Synaptic Transmission

All Science Journal Classification (ASJC) codes

  • Pharmacology

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@article{e99c6743558943feb8a722880cf9c641,
title = "Interaction between cannabinoid CB(1) receptors and endogenous ATP in the control of spontaneous mechanical activity in mouse ileum",
abstract = "Background and purpose: Although it is well accepted that cannabinoids modulate intestinal motility by reducing cholinergic neurotransmission mediated by CB1 receptors, it is not known whether the endocannabinoids are involved in more complex circuits and if they interact with other systems. The aim of the present study was to examine possible interactions between cannabinoid CB1 receptors and purines in the control of spontaneous contractility of longitudinal muscle in mouse ileum.Experimental approach: The mechanical activity of longitudinally oriented ileal segments from mice was recorded as isometric contractions.Key results: The selective CB1 receptor agonist, N-(2-chloroethyl)5,8,11,14-eicosaetraenamide (ACEA) reduced, concentration dependently, spontaneous contractions in mouse ileum. This effect was almost abolished by tetrodotoxin (TTX) or atropine. Inhibition by ACEA was not affected by theophylline (P1 receptor antagonist) or by P2Y receptor desensitization with adenosine5′[b-thio]diphosphate trilithium salt, but was significantly reversed by pyridoxal phosphate-6-azo(benzene-2,4-disulphonic acid) (P2 receptor antagonist), by P2X receptor desensitization with a,b-methyleneadenosine 5′-triphosphate lithiumsalt (a,b-MeATP) or by 8,8′-[carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino) bis(1,3,5-naphthalenetrisulphonic acid)] (P2X receptor antagonist). Contractile responses to a,b-MeATP (P2X receptor agonist) were virtually abolished by TTX or atropine, suggesting that they were mediated by acetylcholine released from neurones, and significantly reduced by ACEA.Conclusion and implications: In mouse ileum, activation of CB1 receptors, apart from reducing acetylcholine release from cholinergic nerves, was able to modulate negatively, endogenous purinergic effects, mediated by P2X receptors, on cholinergic neurons. Our study provides evidence for a role of cannabinoids in the modulation of interneuronal purinergic transmission.",
keywords = "ATP, CB(1) receptors, P2X receptors: enteric nervous system, cannabinoids, cholinergic transmission, purines",
author = "Zizzo, {Maria Grazia} and Flavia Mule' and Sara Baldassano and Serio, {Rosa Maria}",
year = "2009",
language = "English",
volume = "158",
pages = "243--251",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Interaction between cannabinoid CB(1) receptors and endogenous ATP in the control of spontaneous mechanical activity in mouse ileum

AU - Zizzo, Maria Grazia

AU - Mule', Flavia

AU - Baldassano, Sara

AU - Serio, Rosa Maria

PY - 2009

Y1 - 2009

N2 - Background and purpose: Although it is well accepted that cannabinoids modulate intestinal motility by reducing cholinergic neurotransmission mediated by CB1 receptors, it is not known whether the endocannabinoids are involved in more complex circuits and if they interact with other systems. The aim of the present study was to examine possible interactions between cannabinoid CB1 receptors and purines in the control of spontaneous contractility of longitudinal muscle in mouse ileum.Experimental approach: The mechanical activity of longitudinally oriented ileal segments from mice was recorded as isometric contractions.Key results: The selective CB1 receptor agonist, N-(2-chloroethyl)5,8,11,14-eicosaetraenamide (ACEA) reduced, concentration dependently, spontaneous contractions in mouse ileum. This effect was almost abolished by tetrodotoxin (TTX) or atropine. Inhibition by ACEA was not affected by theophylline (P1 receptor antagonist) or by P2Y receptor desensitization with adenosine5′[b-thio]diphosphate trilithium salt, but was significantly reversed by pyridoxal phosphate-6-azo(benzene-2,4-disulphonic acid) (P2 receptor antagonist), by P2X receptor desensitization with a,b-methyleneadenosine 5′-triphosphate lithiumsalt (a,b-MeATP) or by 8,8′-[carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino) bis(1,3,5-naphthalenetrisulphonic acid)] (P2X receptor antagonist). Contractile responses to a,b-MeATP (P2X receptor agonist) were virtually abolished by TTX or atropine, suggesting that they were mediated by acetylcholine released from neurones, and significantly reduced by ACEA.Conclusion and implications: In mouse ileum, activation of CB1 receptors, apart from reducing acetylcholine release from cholinergic nerves, was able to modulate negatively, endogenous purinergic effects, mediated by P2X receptors, on cholinergic neurons. Our study provides evidence for a role of cannabinoids in the modulation of interneuronal purinergic transmission.

AB - Background and purpose: Although it is well accepted that cannabinoids modulate intestinal motility by reducing cholinergic neurotransmission mediated by CB1 receptors, it is not known whether the endocannabinoids are involved in more complex circuits and if they interact with other systems. The aim of the present study was to examine possible interactions between cannabinoid CB1 receptors and purines in the control of spontaneous contractility of longitudinal muscle in mouse ileum.Experimental approach: The mechanical activity of longitudinally oriented ileal segments from mice was recorded as isometric contractions.Key results: The selective CB1 receptor agonist, N-(2-chloroethyl)5,8,11,14-eicosaetraenamide (ACEA) reduced, concentration dependently, spontaneous contractions in mouse ileum. This effect was almost abolished by tetrodotoxin (TTX) or atropine. Inhibition by ACEA was not affected by theophylline (P1 receptor antagonist) or by P2Y receptor desensitization with adenosine5′[b-thio]diphosphate trilithium salt, but was significantly reversed by pyridoxal phosphate-6-azo(benzene-2,4-disulphonic acid) (P2 receptor antagonist), by P2X receptor desensitization with a,b-methyleneadenosine 5′-triphosphate lithiumsalt (a,b-MeATP) or by 8,8′-[carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino) bis(1,3,5-naphthalenetrisulphonic acid)] (P2X receptor antagonist). Contractile responses to a,b-MeATP (P2X receptor agonist) were virtually abolished by TTX or atropine, suggesting that they were mediated by acetylcholine released from neurones, and significantly reduced by ACEA.Conclusion and implications: In mouse ileum, activation of CB1 receptors, apart from reducing acetylcholine release from cholinergic nerves, was able to modulate negatively, endogenous purinergic effects, mediated by P2X receptors, on cholinergic neurons. Our study provides evidence for a role of cannabinoids in the modulation of interneuronal purinergic transmission.

KW - ATP

KW - CB(1) receptors

KW - P2X receptors: enteric nervous system

KW - cannabinoids

KW - cholinergic transmission

KW - purines

UR - http://hdl.handle.net/10447/45615

M3 - Article

VL - 158

SP - 243

EP - 251

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

ER -