PMID- 35872047
OWN - NLM
STAT- MEDLINE
DCOM- 20220816
LR  - 20220816
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 364
DP  - 2022 Sep 1
TI  - Supplemental treatment to atropine improves the efficacy to reverse nerve agent 
      induced bronchoconstriction.
PG  - 110061
LID - S0009-2797(22)00266-6 [pii]
LID - 10.1016/j.cbi.2022.110061 [doi]
AB  - Exposure to highly toxic organophosphorus compounds causes inhibition of the 
      enzyme acetylcholinesterase resulting in a cholinergic toxidrome and innervation 
      of receptors in the neuromuscular junction may cause life-threatening respiratory 
      effects. The involvement of several receptor systems was therefore examined for 
      their impact on bronchoconstriction using an ex vivo rat precision-cut lung slice 
      (PCLS) model. The ability to recover airways with therapeutics following nerve 
      agent exposure was determined by quantitative analyses of muscle contraction. 
      PCLS exposed to nicotine resulted in a dose-dependent bronchoconstriction. The 
      neuromuscular nicotinic antagonist tubocurarine counteracted the nicotine-induced 
      bronchoconstriction but not the ganglion blocker mecamylamine or the common 
      muscarinic antagonist atropine. Correspondingly, atropine demonstrated a 
      significant airway relaxation following ACh-exposure while tubocurarine did not. 
      Atropine, the M3 muscarinic receptor antagonist 4-DAMP, tubocurarine, the 
      beta(2)-adrenergic receptor agonist formoterol, the Na(+)-channel blocker 
      tetrodotoxin and the K(+)(ATP)-channel opener cromakalim all significantly 
      decreased airway contractions induced by electric field stimulation. Following 
      VX-exposure, treatment with atropine and the Ca(2+)-channel blocker magnesium 
      sulfate resulted in significant airway relaxation. Formoterol, cromakalim and 
      magnesium sulfate administered in combinations with atropine demonstrated an 
      additive effect. In conclusion, the present study demonstrated improved airway 
      function following nerve agent exposure by adjunct treatment to the standard 
      therapy of atropine.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Wigenstam, Elisabeth
AU  - Wigenstam E
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden.
FAU - Artursson, Elisabet
AU  - Artursson E
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden.
FAU - Bucht, Anders
AU  - Bucht A
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden.
FAU - Thors, Lina
AU  - Thors L
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden. 
      Electronic address: lina.thors@foi.se.
LA  - eng
PT  - Journal Article
DEP - 20220722
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Nerve Agents)
RN  - 0G4X367WA3 (Cromakalim)
RN  - 6M3C89ZY6R (Nicotine)
RN  - 7487-88-9 (Magnesium Sulfate)
RN  - 7C0697DR9I (Atropine)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - W34SHF8J2K (Formoterol Fumarate)
RN  - W9YXS298BM (Tubocurarine)
SB  - IM
MH  - Acetylcholinesterase
MH  - Animals
MH  - Atropine/pharmacology
MH  - *Bronchoconstriction
MH  - Cromakalim/pharmacology
MH  - Electric Stimulation
MH  - Formoterol Fumarate/pharmacology
MH  - Magnesium Sulfate/pharmacology
MH  - Muscarinic Antagonists/pharmacology
MH  - Muscle Contraction
MH  - *Nerve Agents/pharmacology
MH  - Nicotine/pharmacology
MH  - Rats
MH  - Tubocurarine/pharmacology
OTO - NOTNLM
OT  - Airway contractions
OT  - Medical treatment
OT  - Nerve agents
OT  - Neuromuscular junction
OT  - Precision-cut lung slices
EDAT- 2022/07/26 06:00
MHDA- 2022/08/17 06:00
CRDT- 2022/07/25 01:47
PHST- 2022/05/11 00:00 [received]
PHST- 2022/06/23 00:00 [revised]
PHST- 2022/07/13 00:00 [accepted]
PHST- 2022/07/26 06:00 [pubmed]
PHST- 2022/08/17 06:00 [medline]
PHST- 2022/07/25 01:47 [entrez]
AID - S0009-2797(22)00266-6 [pii]
AID - 10.1016/j.cbi.2022.110061 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2022 Sep 1;364:110061. doi: 10.1016/j.cbi.2022.110061. Epub 
      2022 Jul 22.