Cannabinoid 1 (CB1) receptors coupled to cholinergic motorneurones inhibit neurogenic circular muscle contractility in the human colon

Authors

  • Nicholas M Hinds,

    1. School of Chemical & Biomedical Sciences, Faculty of Arts Health & Sciences, Central Queensland University, Bruce Highway, Rockhampton, QLD 4702, Australia
    Search for more papers by this author
  • Katja Ullrich,

    1. Faculty of Health Sciences & Medicine, Bond University, Robina, QLD 4229, Australia
    Search for more papers by this author
  • Scott D Smid

    Corresponding author
    1. Faculty of Health Sciences & Medicine, Bond University, Robina, QLD 4229, Australia
      Discipline of Pharmacology, School of Medical Sciences, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5005, Australia. E-mail: scott.smid@adelaide.edu.au
    Search for more papers by this author

Discipline of Pharmacology, School of Medical Sciences, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5005, Australia. E-mail: scott.smid@adelaide.edu.au

Abstract

  • 1The effects of cannabinoid subtype 1 (CB1) receptor activation were determined on smooth muscle, inhibitory and excitatory motorneuronal function in strips of human colonic longitudinal muscle (LM) and circular muscle (CM) in vitro.
  • 2Electrical field stimulation (EFS; 0.5–20 Hz, 50 V) evoked a relaxation in LM and CM precontracted with a neurokinin-2 (NK-2) selective receptor agonist (β-ala8-neurokinin A; 10−6 M) in the presence of atropine (10−6 M); this was unaltered following pretreatment with the CB1-receptor selective agonist arachidonyl-2-chloroethylamide (ACEA; 10−6 M).
  • 3In the presence of nitric oxide synthase blockade with N-nitro-L-arginine (10−4 M), EFS evoked a frequency-dependent ‘on-contraction’ during stimulation and an ‘off-contraction’ following stimulus cessation. On-contractions were significantly inhibited in CM strips by pretreatment with ACEA (10−6 M). These inhibitory effects were reversed in the presence of the CB1 receptor-selective antagonist N-(piperidine-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (10−7 M).
  • 4ACEA did not alter LM or CM contractile responses to acetylcholine or NK-2 receptor-evoked contraction.
  • 5Immunohistochemical studies revealed a colocalisation of CB1 receptors to cholinergic neurones in the human colon based on colabelling with choline acetyltransferase, in addition to CB1 receptor labelling in unidentified structures in the CM.
  • 6In conclusion, activation of CB1 receptors coupled to cholinergic motorneurones selectively and reversibly inhibits excitatory nerve transmission in colonic human colonic CM. These results provide evidence of a direct role for cannabinoids in the modulation of motor activity in the human colon by coupling to cholinergic motorneurones.

British Journal of Pharmacology (2006) 148, 191–199. doi:10.1038/sj.bjp.0706710

Ancillary