TY - JOUR
T1 - Colonic motor dysfunctions in a mouse model of high-fat diet-induced obesity
T2 - an involvement of A2B adenosine receptors
AU - Antonioli, Luca
AU - Pellegrini, Carolina
AU - Fornai, Matteo
AU - Tirotta, Erika
AU - Gentile, Daniela
AU - Benvenuti, Laura
AU - Giron, Maria Cecilia
AU - Caputi, Valentina
AU - Marsilio, Ilaria
AU - Orso, Genny
AU - Bernardini, Nunzia
AU - Segnani, Cristina
AU - Ippolito, Chiara
AU - Csóka, Balázs
AU - Németh, Zoltán H.
AU - Haskó, György
AU - Scarpignato, Carmelo
AU - Blandizzi, Corrado
AU - Colucci, Rocchina
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Adenosine A2B receptors (A2BR) regulate several enteric functions. However, their implication in the pathophysiology of intestinal dysmotility associated with high-fat diet (HFD)-induced obesity has not been elucidated. We investigated the expression of A2BR in mouse colon and their role in the mechanisms underlying the development of enteric dysmotility associated with obesity. Wild-type C57BL/6J mice were fed with HFD (60% kcal from fat) or normocaloric diet (NCD; 18% kcal from fat) for 8 weeks. Colonic A2BR localization was examined by immunofluorescence. The role of A2BR in the control of colonic motility was examined in functional experiments on longitudinal muscle preparations (LMPs). In NCD mice, A2BR were predominantly located in myenteric neurons; in HFD animals, their expression increased throughout the neuromuscular layer. Functionally, the A2BR antagonist MRS1754 enhanced electrically induced NK1-mediated tachykininergic contractions in LMPs from HFD mice, while it was less effective in tissues from NCD mice. The A2B receptor agonist BAY 60-6583 decreased colonic tachykininergic contractions in LMPs, with higher efficacy in preparations from obese mice. Both A2BR ligands did not affect contractions elicited by exogenous substance P. Obesity is related with a condition of colonic inflammation, leading to an increase of A2BR expression. A2BR, modulating the activity of excitatory tachykininergic nerves, participate to the enteric dysmotility associated with obesity.
AB - Adenosine A2B receptors (A2BR) regulate several enteric functions. However, their implication in the pathophysiology of intestinal dysmotility associated with high-fat diet (HFD)-induced obesity has not been elucidated. We investigated the expression of A2BR in mouse colon and their role in the mechanisms underlying the development of enteric dysmotility associated with obesity. Wild-type C57BL/6J mice were fed with HFD (60% kcal from fat) or normocaloric diet (NCD; 18% kcal from fat) for 8 weeks. Colonic A2BR localization was examined by immunofluorescence. The role of A2BR in the control of colonic motility was examined in functional experiments on longitudinal muscle preparations (LMPs). In NCD mice, A2BR were predominantly located in myenteric neurons; in HFD animals, their expression increased throughout the neuromuscular layer. Functionally, the A2BR antagonist MRS1754 enhanced electrically induced NK1-mediated tachykininergic contractions in LMPs from HFD mice, while it was less effective in tissues from NCD mice. The A2B receptor agonist BAY 60-6583 decreased colonic tachykininergic contractions in LMPs, with higher efficacy in preparations from obese mice. Both A2BR ligands did not affect contractions elicited by exogenous substance P. Obesity is related with a condition of colonic inflammation, leading to an increase of A2BR expression. A2BR, modulating the activity of excitatory tachykininergic nerves, participate to the enteric dysmotility associated with obesity.
KW - A receptors
KW - Colonic motor dysfunctions
KW - Obesity
KW - Substance P
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U2 - 10.1007/s11302-017-9577-0
DO - 10.1007/s11302-017-9577-0
M3 - Article
AN - SCOPUS:85028570103
VL - 13
SP - 497
EP - 510
JO - Purinergic Signalling
JF - Purinergic Signalling
SN - 1573-9538
IS - 4
ER -