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Involvement of CB1 and CB2 receptors in the modulation of cholinergic neurotransmission in mouse gastric preparations.

Abstract

While most of the studies concerning the role of cannabinoids on gastric motility have focused the attention on the gastric emptying in in vivo animal models, there is little information about the cannabinoid peripheral influence in the stomach. In addition, the functional features of CB2 receptors in the gastrointestinal tract have been poorly characterized. The purpose of the present study was to investigate the effects of cannabinoid drugs on the excitatory cholinergic and inhibitory non-adrenergic non-cholinergic (NANC) neurotransmission in mouse isolated gastric preparations. Intraluminal pressure from isolated whole stomach was recorded and mechanical responses induced by electrical field stimulation (EFS) were analyzed in different experimental conditions. EFS (0.5ms duration, supramaximal voltage, in trains of 5s, 2-16Hz) caused a cholinergic contraction, which was abolished by atropine or tetrodotoxin (TTX). The cannabinoid receptor agonist, WIN 55,212-2, the endogenous ligand, anandamide, the selective CB1 receptor agonist ACEA, and the selective CB2 receptor agonists, JWH015 and JWH133, produced a concentration-dependent reduction of the EFS-evoked cholinergic contractions. SR141716A, CB1 receptor antagonist, significantly attenuated the inhibitory effects induced by WIN 55,212-2, anandamide or ACEA, without affecting those caused by JWH133. AM630, CB2 receptor antagonist, reduced the inhibitory effects induced by WIN 55,212-2, anandamide, JWH015 or JWH133, without affecting those caused by ACEA. The joint application of SR141716A and AM630 was able of fully preventing the WIN 55,212-2 and anandamide actions. The cannabinoid antagonists failed per se to affect the neurally evoked responses. Cannabinoids did not modify the contractions produced by exogenous carbachol. In the presence of atropine and guanethidine (NANC conditions) EFS-induced TTX-sensitive relaxation consisting in an early and rapid component followed by a second slow phase, which were unaffected by cannabinoid drugs. In conclusion, the present results suggest that cannabinoids play a prejunctional modulatory role on the cholinergic excitatory transmission without affecting the NANC inhibitory transmission. In addition, this study provides experimental evidence that also the activation of CB2 receptors is able to reduce cholinergic neurotransmission in the mouse stomach.

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  • Authors+Show Affiliations

    ,

    Dipartimento di Biologia cellulare e dello Sviluppo, Viale delle Scienze, Università di Palermo, 90128 Palermo, Italy. fmule@unipa.it

    , ,

    Source

    Pharmacological research 56:3 2007 Sep pg 185-92

    MeSH

    Animals
    Arachidonic Acids
    Benzoxazines
    Cannabinoid Receptor Modulators
    Cannabinoids
    Cholinergic Fibers
    Electric Stimulation
    Endocannabinoids
    Excitatory Postsynaptic Potentials
    Gastrointestinal Motility
    In Vitro Techniques
    Indoles
    Inhibitory Postsynaptic Potentials
    Male
    Mice
    Mice, Inbred C57BL
    Morpholines
    Naphthalenes
    Neuromuscular Junction
    Piperidines
    Polyunsaturated Alkamides
    Pyrazoles
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Receptors, Presynaptic
    Rimonabant
    Stomach
    Synaptic Transmission

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17656103

    Citation

    Mulè, Flavia, et al. "Involvement of CB1 and CB2 Receptors in the Modulation of Cholinergic Neurotransmission in Mouse Gastric Preparations." Pharmacological Research, vol. 56, no. 3, 2007, pp. 185-92.
    Mulè F, Amato A, Baldassano S, et al. Involvement of CB1 and CB2 receptors in the modulation of cholinergic neurotransmission in mouse gastric preparations. Pharmacol Res. 2007;56(3):185-92.
    Mulè, F., Amato, A., Baldassano, S., & Serio, R. (2007). Involvement of CB1 and CB2 receptors in the modulation of cholinergic neurotransmission in mouse gastric preparations. Pharmacological Research, 56(3), pp. 185-92.
    Mulè F, et al. Involvement of CB1 and CB2 Receptors in the Modulation of Cholinergic Neurotransmission in Mouse Gastric Preparations. Pharmacol Res. 2007;56(3):185-92. PubMed PMID: 17656103.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Involvement of CB1 and CB2 receptors in the modulation of cholinergic neurotransmission in mouse gastric preparations. AU - Mulè,Flavia, AU - Amato,Antonella, AU - Baldassano,Sara, AU - Serio,Rosa, Y1 - 2007/06/21/ PY - 2007/05/04/received PY - 2007/06/14/revised PY - 2007/06/15/accepted PY - 2007/7/28/pubmed PY - 2007/11/2/medline PY - 2007/7/28/entrez SP - 185 EP - 92 JF - Pharmacological research JO - Pharmacol. Res. VL - 56 IS - 3 N2 - While most of the studies concerning the role of cannabinoids on gastric motility have focused the attention on the gastric emptying in in vivo animal models, there is little information about the cannabinoid peripheral influence in the stomach. In addition, the functional features of CB2 receptors in the gastrointestinal tract have been poorly characterized. The purpose of the present study was to investigate the effects of cannabinoid drugs on the excitatory cholinergic and inhibitory non-adrenergic non-cholinergic (NANC) neurotransmission in mouse isolated gastric preparations. Intraluminal pressure from isolated whole stomach was recorded and mechanical responses induced by electrical field stimulation (EFS) were analyzed in different experimental conditions. EFS (0.5ms duration, supramaximal voltage, in trains of 5s, 2-16Hz) caused a cholinergic contraction, which was abolished by atropine or tetrodotoxin (TTX). The cannabinoid receptor agonist, WIN 55,212-2, the endogenous ligand, anandamide, the selective CB1 receptor agonist ACEA, and the selective CB2 receptor agonists, JWH015 and JWH133, produced a concentration-dependent reduction of the EFS-evoked cholinergic contractions. SR141716A, CB1 receptor antagonist, significantly attenuated the inhibitory effects induced by WIN 55,212-2, anandamide or ACEA, without affecting those caused by JWH133. AM630, CB2 receptor antagonist, reduced the inhibitory effects induced by WIN 55,212-2, anandamide, JWH015 or JWH133, without affecting those caused by ACEA. The joint application of SR141716A and AM630 was able of fully preventing the WIN 55,212-2 and anandamide actions. The cannabinoid antagonists failed per se to affect the neurally evoked responses. Cannabinoids did not modify the contractions produced by exogenous carbachol. In the presence of atropine and guanethidine (NANC conditions) EFS-induced TTX-sensitive relaxation consisting in an early and rapid component followed by a second slow phase, which were unaffected by cannabinoid drugs. In conclusion, the present results suggest that cannabinoids play a prejunctional modulatory role on the cholinergic excitatory transmission without affecting the NANC inhibitory transmission. In addition, this study provides experimental evidence that also the activation of CB2 receptors is able to reduce cholinergic neurotransmission in the mouse stomach. SN - 1043-6618 UR - https://www.unboundmedicine.com/medline/citation/17656103/Involvement_of_CB1_and_CB2_receptors_in_the_modulation_of_cholinergic_neurotransmission_in_mouse_gastric_preparations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(07)00113-2 DB - PRIME DP - Unbound Medicine ER -