Basic–Alimentary TractCannabinoid receptor agonism inhibits transient lower esophageal sphincter relaxations and reflux in dogs☆,☆☆
Section snippets
Transient LES relaxations in dogs
All studies were performed with the approval and within the guidelines of the Animal Ethics Committees of the Göteborg region. Eleven adult male and female Labrador retrievers were recruited to the study. They were retained with the inclusion criterion that the average number of TLESRs should not be less than 4 every 45 minutes during stimulation using parameters detailed later. Cervical esophagostomies were made and after a recovery period, the dogs were used in different drug-screening
Effects of CBR ligands on TLESRs and related parameters
The average number of TLESRs, reflux episodes and other motility parameters for all the control experiments with intravenous (IV) administration are noted in Table 1 (11 dogs, n = 66). The results are based on all IV control experiments in 11 dogs (n = 66) used in the present study.TLESRs/45 min Latency to first TLESR (min) Swallows/45 min Reflux episodes/45 min 5.7 ± 0.1 4.1 ± 0.3 13.5 ± 1.0 3.7 ± 0.2
Discussion
The present study shows for the first time that CBRs inhibit TLESR and gastroesophageal reflux. The potency of the CBR agonist WIN 55,212-2 we observed was high in comparison with previously reported effects on emesis. For instance, the antiemetic ED50 of WIN 55,212-2 is approximately 1 mg/kg.12, 13 However, WIN 55,212-2 blocked opioid-induced emesis in ferrets with an ED50 of 0.03 mg/kg.11
The agonist reduced the rate of TLESRs without altering their shape (duration, simultaneous esophageal
References (33)
- et al.
Transient lower esophageal sphincter relaxation
Gastroenterology
(1995) - et al.
Activation of the GABAB receptor inhibits transient lower esophageal sphincter relaxations in dogs
Gastroenterology
(1999) - et al.
Control of transient lower esophageal sphincter relaxations and reflux by the GABAB agonist baclofen in normal subjects
Gastroenterology
(2000) Pharmacology of cannabinoid CB1 and CB2 receptors
Pharmacol Ther
(1997)- et al.
Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret
Gastroenterology
(2001) The cannabinoid CB1 receptor antagonist SR141716A reverses the antiemetic and motor depressant actions of WIN 55, 212-2
Eur J Pharmacol
(2001)- et al.
Effects of antagonism of NMDA receptors on transient lower esophageal sphincter relaxations in the dog
Eur J Pharmacol
(2001) Evidence for the presence of CB1 cannabinoid receptors on peripheral neurones and for the existence of neuronal non-CB1 cannabinoid receptors
Life Sci
(1999)- et al.
Effect of atropine on the frequency of reflux and transient lower esophageal sphincter relaxation in normal subjects
Gastroenterology
(1995) - et al.
Cholecystokinin and nitric oxide in transient lower esophageal sphincter relaxations to gastric distention in dogs
Gastroenterology
(1994)
Effect of morphine on gastroesophageal reflux and transient lower esophageal sphincter relaxation
Gastroenterology
Neuronal responses to cannabinoid receptor ligands in the solitary tract nucleus
Eur J Pharmacol
Cannabinonid CB1 receptor expression in rat spinal cord
Mol Cell Neurosci
Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects
J Clin Invest
Inhibition of transient LES relaxations and reflux in ferrets by GABA receptor agonists
Am J Physiol
Control of transient lower oesophageal sphincter relaxations and reflux by the GABAB agonist baclofen in patients with gastro-oesophageal reflux disease
Gut
Cited by (91)
Management of cannabinoid hyperemesis syndrome—is it more than just avoiding cannabis use?
2022, Cyclic Vomiting Syndrome and Cannabinoid HyperemesisCannabinoid pharmacology and therapy in gut disorders
2018, Biochemical PharmacologyCitation Excerpt :CB1 receptors have been located in brain areas related to the triggering of TLESRs in the ferret [37] and the expression of CB1 mRNA in patients with non-erosive esophageal reflux disease (NERD) was increased compared with erosive esophagitis [38]. Also, cannabinoid agonists reduced the occurrence of TLESRs in dogs and healthy volunteers [39,40]. Interestingly, the use of a CB1 receptor antagonist (rimonabant) in healthy human subjects decreased TLESRs.
Pathophysiological Mechanisms of Gastrointestinal Toxicity
2018, Comprehensive Toxicology: Third EditionMedical Cannabis for the Treatment of Inflammatory Bowel Disease
2017, Handbook of Cannabis and Related Pathologies: Biology, Pharmacology, Diagnosis, and TreatmentCannabinoids and Effects on the Gastrointestinal Tract: A Focus on Motility
2017, Handbook of Cannabis and Related Pathologies: Biology, Pharmacology, Diagnosis, and TreatmentEndocannabinoid signaling at the periphery: 50 years after THC
2015, Trends in Pharmacological Sciences
- ☆
Address requests for reprints to: Anders Lehmann, Ph.D., Gastrointestinal Biology, Integrative Pharmacology, AstraZeneca R&D Mölndal, S-431 83 Mölndal, Sweden. e-mail [email protected]; fax: (46) 31 776 3747.
- ☆☆
Supported by AstraZeneca R&D Mölndal.