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Evidence for a modulatory role of cannabinoids on the excitatory NANC neurotransmission in mouse colon.

Abstract

It is well accepted that endogenous cannabinoids and CB1 receptors are involved in the regulation of smooth muscle contractility and intestinal motility, through a mechanism mainly related to reduction of acetylcholine release from cholinergic nerve endings. Because, few data exist on a possible modulatory action of the cannabinoid agents on the non-adrenergic non-cholinergic (NANC) excitatory and inhibitory neurotransmission, the aim of the present study was to investigate the effects of cannabinoid drugs on the NANC responses elicited by electrical field stimulation (EFS) in the circular muscle of mouse proximal colon. Colonic contractions were monitored as changes in endoluminal pressure. In NANC conditions, EFS evoked TTX-sensitive responses, characterized by a relaxation, nitrergic in origin, followed by a contraction. The EFS-evoked contraction was significantly reduced by SR48968, NK2 receptor antagonist, and abolished by co-administration of SR48968 and SR140333, NK1 receptor antagonist, suggesting that it was due to release of tachykinins. The cannabinoid receptor synthetic agonist, WIN55,212-2, the putative endogenous ligand, anandamide, the selective CB1 receptor agonist ACEA, but not the selective CB2 receptor agonist JWH-015, produced a concentration-dependent reduction of the NANC contractile responses, without affecting the NANC relaxation. ACEA or anandamide did not modify the contractions induced by exogenous [beta-Ala(8)]-NKA(4-10), agonist of NK2 receptors. The selective antagonist of CB1 receptors, SR141716A, per se failed to affect the EFS-evoked responses, but antagonized the inhibitory effects of WIN55,212-2, anandamide and ACEA on NANC contractile responses. AM630, CB2 receptor antagonist, did not modify the inhibitory effects of WIN55,212-2 or anandamide. URB597, inhibitor of the fatty acid amide hydrolase, enzyme which catalyze the hydrolysis of anandamide, was without any effect on the NANC evoked responses. We conclude that the activation of prejunctional CB1 receptors produces inhibition of NANC contractile responses in mouse colonic preparations. However, endogenous ligands do not seem to modulate tonically the NANC transmission in mouse colon.

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  • Authors+Show Affiliations

    ,

    Dipartimento di Biologia cellulare e dello Sviluppo, Università di Palermo, 90128 Palermo, Italia. fmule@unipa.it

    , ,

    Source

    Pharmacological research 56:2 2007 Aug pg 132-9

    MeSH

    Animals
    Arachidonic Acids
    Benzoxazines
    Cannabinoid Receptor Modulators
    Cannabinoids
    Colon
    Dose-Response Relationship, Drug
    Electric Stimulation
    Endocannabinoids
    Enteric Nervous System
    Excitatory Postsynaptic Potentials
    Gastrointestinal Motility
    In Vitro Techniques
    Indoles
    Inhibitory Postsynaptic Potentials
    Mice
    Mice, Inbred C57BL
    Morpholines
    Naphthalenes
    Neuromuscular Junction
    Piperidines
    Polyunsaturated Alkamides
    Pyrazoles
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Receptors, Tachykinin
    Rimonabant
    Synaptic Transmission
    Tachykinins

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    17574859

    Citation

    Mulè, Flavia, et al. "Evidence for a Modulatory Role of Cannabinoids On the Excitatory NANC Neurotransmission in Mouse Colon." Pharmacological Research, vol. 56, no. 2, 2007, pp. 132-9.
    Mulè F, Amato A, Baldassano S, et al. Evidence for a modulatory role of cannabinoids on the excitatory NANC neurotransmission in mouse colon. Pharmacol Res. 2007;56(2):132-9.
    Mulè, F., Amato, A., Baldassano, S., & Serio, R. (2007). Evidence for a modulatory role of cannabinoids on the excitatory NANC neurotransmission in mouse colon. Pharmacological Research, 56(2), pp. 132-9.
    Mulè F, et al. Evidence for a Modulatory Role of Cannabinoids On the Excitatory NANC Neurotransmission in Mouse Colon. Pharmacol Res. 2007;56(2):132-9. PubMed PMID: 17574859.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Evidence for a modulatory role of cannabinoids on the excitatory NANC neurotransmission in mouse colon. AU - Mulè,Flavia, AU - Amato,Antonella, AU - Baldassano,Sara, AU - Serio,Rosa, Y1 - 2007/05/10/ PY - 2007/03/15/received PY - 2007/04/26/revised PY - 2007/04/27/accepted PY - 2007/6/19/pubmed PY - 2007/11/2/medline PY - 2007/6/19/entrez SP - 132 EP - 9 JF - Pharmacological research JO - Pharmacol. Res. VL - 56 IS - 2 N2 - It is well accepted that endogenous cannabinoids and CB1 receptors are involved in the regulation of smooth muscle contractility and intestinal motility, through a mechanism mainly related to reduction of acetylcholine release from cholinergic nerve endings. Because, few data exist on a possible modulatory action of the cannabinoid agents on the non-adrenergic non-cholinergic (NANC) excitatory and inhibitory neurotransmission, the aim of the present study was to investigate the effects of cannabinoid drugs on the NANC responses elicited by electrical field stimulation (EFS) in the circular muscle of mouse proximal colon. Colonic contractions were monitored as changes in endoluminal pressure. In NANC conditions, EFS evoked TTX-sensitive responses, characterized by a relaxation, nitrergic in origin, followed by a contraction. The EFS-evoked contraction was significantly reduced by SR48968, NK2 receptor antagonist, and abolished by co-administration of SR48968 and SR140333, NK1 receptor antagonist, suggesting that it was due to release of tachykinins. The cannabinoid receptor synthetic agonist, WIN55,212-2, the putative endogenous ligand, anandamide, the selective CB1 receptor agonist ACEA, but not the selective CB2 receptor agonist JWH-015, produced a concentration-dependent reduction of the NANC contractile responses, without affecting the NANC relaxation. ACEA or anandamide did not modify the contractions induced by exogenous [beta-Ala(8)]-NKA(4-10), agonist of NK2 receptors. The selective antagonist of CB1 receptors, SR141716A, per se failed to affect the EFS-evoked responses, but antagonized the inhibitory effects of WIN55,212-2, anandamide and ACEA on NANC contractile responses. AM630, CB2 receptor antagonist, did not modify the inhibitory effects of WIN55,212-2 or anandamide. URB597, inhibitor of the fatty acid amide hydrolase, enzyme which catalyze the hydrolysis of anandamide, was without any effect on the NANC evoked responses. We conclude that the activation of prejunctional CB1 receptors produces inhibition of NANC contractile responses in mouse colonic preparations. However, endogenous ligands do not seem to modulate tonically the NANC transmission in mouse colon. SN - 1043-6618 UR - https://www.unboundmedicine.com/medline/citation/17574859/Evidence_for_a_modulatory_role_of_cannabinoids_on_the_excitatory_NANC_neurotransmission_in_mouse_colon_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(07)00098-9 DB - PRIME DP - Unbound Medicine ER -