Agonist-dependent development of delta opioid receptor tolerance in the colon.
Analgesics, Opioid
/ pharmacology
Animals
Benzamides
/ pharmacology
Colon
/ drug effects
Drug Tolerance
Electric Stimulation
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Muscle Contraction
/ drug effects
Neurons
/ metabolism
Piperazines
/ pharmacology
Receptors, Opioid, delta
/ agonists
Receptors, Opioid, mu
/ agonists
Colon motility
Endocytosis
Enteric nervous system
GPCR regulation
Opioid receptor
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
20
11
2018
accepted:
18
03
2019
revised:
26
02
2019
pubmed:
25
3
2019
medline:
31
7
2019
entrez:
25
3
2019
Statut:
ppublish
Résumé
The use of opioid analgesics is severely limited due to the development of intractable constipation, mediated through activation of mu opioid receptors (MOR) expressed by enteric neurons. The related delta opioid receptor (DOR) is an emerging therapeutic target for chronic pain, depression and anxiety. Whether DOR agonists also promote sustained inhibition of colonic transit is unknown. This study examined acute and chronic tolerance to SNC80 and ARM390, which were full and partial DOR agonists in neural pathways controlling colonic motility, respectively. Excitatory pathways developed acute and chronic tolerance to SNC80, whereas only chronic tolerance developed in inhibitory pathways. Both pathways remained functional after acute or chronic ARM390 exposure. Propagating colonic motor patterns were significantly reduced after acute or chronic SNC80 treatment, but not by ARM390 pre-treatment. These findings demonstrate that SNC80 has a prolonged inhibitory effect on propagating colonic motility. ARM390 had no effect on motor patterns and thus may have fewer gastrointestinal side-effects.
Identifiants
pubmed: 30904952
doi: 10.1007/s00018-019-03077-6
pii: 10.1007/s00018-019-03077-6
doi:
Substances chimiques
Analgesics, Opioid
0
Benzamides
0
Piperazines
0
Receptors, Opioid, delta
0
Receptors, Opioid, mu
0
4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
156727-74-1
Types de publication
Journal Article
Langues
eng
Pagination
3033-3050Subventions
Organisme : National Health and Medical Research Council
ID : 1049730
Organisme : National Health and Medical Research Council
ID : 1121029
Organisme : National Health and Medical Research Council
ID : 1083480
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