TY - JOUR
T1 - Inhalation anaesthetic isoflurane inhibits the muscarinic cation current and carbachol-induced gastrointestinal smooth muscle contractions
AU - Dryn, Dariia
AU - Luo, Jialie
AU - Melnyk, Mariia
AU - Zholos, Alexander
AU - Hu, Hongzhen
N1 - Funding Information:
This original research is a part of Ph.D thesis of the first author funded by Washington University School of Medicine in St. Louis (NIH grants RO1DK103901 and RO1GM101218 )
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/2/5
Y1 - 2018/2/5
N2 - Gastrointestinal tract motility may be demoted significantly after surgery operations at least in part due to anaesthetic agents, but there is no comprehensive explanation of the molecular mechanism(s) of such adverse effects. Anesthetics are known to interact with various receptors and ion channels including several subtypes of transient receptor potential (TRP) channels. Two members of the canonical subfamily of TRP channels (TRPC), TRPC4 and TRPC6 are Ca2+-permeable cation channels involved in visceral smooth muscle contractility induced by acetylcholine, the primary excitatory neurotransmitter in the gut. In the present study, we aimed to study the effect of anesthetics on muscarinic receptor-mediated excitation and contraction of intestinal smooth muscle. Here we show that muscarinic cation current (mICAT) mediated by TRPC4 and TRPC6 channels in mouse ileal myocytes was strongly inhibited by isoflurane (0.5 mM), one of the most commonly used inhalation anesthetics. Carbachol-activated mICAT was reduced by 63 ± 11% (n = 5), while GTPγS-induced (to bypass muscarinic receptors) current was inhibited by 44 ± 9% (n = 6). Furthermore, carbachol-induced ileum and colon contractions were inhibited by isoflurane by about 30%. We discuss the main sites of isoflurane action, which appear to be G-proteins and muscarinic receptors, rather than TRPC4/6 channels. These results contribute to our better understanding of the signalling pathways affected by inhalation anesthetics, which may cause ileus, and thus may be important for the development of novel treatment strategies during postoperative recovery.
AB - Gastrointestinal tract motility may be demoted significantly after surgery operations at least in part due to anaesthetic agents, but there is no comprehensive explanation of the molecular mechanism(s) of such adverse effects. Anesthetics are known to interact with various receptors and ion channels including several subtypes of transient receptor potential (TRP) channels. Two members of the canonical subfamily of TRP channels (TRPC), TRPC4 and TRPC6 are Ca2+-permeable cation channels involved in visceral smooth muscle contractility induced by acetylcholine, the primary excitatory neurotransmitter in the gut. In the present study, we aimed to study the effect of anesthetics on muscarinic receptor-mediated excitation and contraction of intestinal smooth muscle. Here we show that muscarinic cation current (mICAT) mediated by TRPC4 and TRPC6 channels in mouse ileal myocytes was strongly inhibited by isoflurane (0.5 mM), one of the most commonly used inhalation anesthetics. Carbachol-activated mICAT was reduced by 63 ± 11% (n = 5), while GTPγS-induced (to bypass muscarinic receptors) current was inhibited by 44 ± 9% (n = 6). Furthermore, carbachol-induced ileum and colon contractions were inhibited by isoflurane by about 30%. We discuss the main sites of isoflurane action, which appear to be G-proteins and muscarinic receptors, rather than TRPC4/6 channels. These results contribute to our better understanding of the signalling pathways affected by inhalation anesthetics, which may cause ileus, and thus may be important for the development of novel treatment strategies during postoperative recovery.
KW - G-proteins
KW - Gastrointestinal smooth muscles
KW - General anesthetics
KW - Isoflurane
KW - Muscarinic receptors
KW - TRP channels
UR - http://www.scopus.com/inward/record.url?scp=85038086474&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2017.11.044
DO - 10.1016/j.ejphar.2017.11.044
M3 - Article
C2 - 29198958
AN - SCOPUS:85038086474
SN - 0014-2999
VL - 820
SP - 39
EP - 44
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -