PMID- 22963524
OWN - NLM
STAT- MEDLINE
DCOM- 20130325
LR  - 20211021
IS  - 1746-6148 (Electronic)
IS  - 1746-6148 (Linking)
VI  - 8
DP  - 2012 Sep 10
TI  - Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused 
      by leukotriene C4 in precision cut lung slices in the horse.
PG  - 160
LID - 10.1186/1746-6148-8-160 [doi]
AB  - BACKGROUND: Glucocorticoids have been proven to be effective in the therapy of 
      recurrent airway obstruction (RAO) in horses via systemic as well as local 
      (inhalative) administration. Elective analysis of the effects of this drug on 
      bronchoconstriction in viable lung tissue offers an insight into the mechanism of 
      action of the inflammatory cascade occurring during RAO which is still unclear. 
      The mechanism of action of steroids in treatment of RAO is thought to be induced 
      through classical genomic pathways. We aimed at electively studying the effects 
      of the glucocorticoid beclomethasone dipropionate on equine precision-cut lung 
      slices (PCLS).PCLS were used to analyze ex-vivo effects of beclomethasone on 
      inhibiting bronchoconstriction in the horse. The inhibiting effect was measured 
      through instillation of a known mediator of inflammation and bronchoconstriction, 
      leukotriene C4. For this, the accessory lobes of 13 horses subjected to 
      euthanasia for reasons unrelated to the respiratory apparatus were used to obtain 
      viable lung slices. RESULTS: After 30 minutes of PCLS incubation, beclomethasone 
      showed to significantly inhibit the contraction of the bronchioles after 
      instillation with leukotriene C4. The EC50 values of the two contraction curves 
      (LTC4 with and without BDP) differed significantly from each other (p = 0.002). 
      The possibility of a non-genomic rapid mechanism of action seems likely since 
      transcriptional activities require a longer lag period. CONCLUSIONS: In human 
      neuroendocrinology, high levels of glucocorticoids have been proven to function 
      via a non-genomic mechanism of membrane receptors. The concentration of 
      beclomethasone used on the lung slices in our study can be considered as high. 
      This allows speculation about similar rapid non-genomic mechanisms of high-dosage 
      inhaled glucocorticoids in the lower airways of horses. However, further 
      assessment on a molecular basis is needed to confirm this.
FAU - Fugazzola, Maria
AU  - Fugazzola M
AD  - University of Veterinary Sciences Hanover, Clinic for Horses, Hanover, Germany. 
      maria.fugazzola@gmail.com
FAU - Barton, Ann-Kristin
AU  - Barton AK
FAU - Niedorf, Frank
AU  - Niedorf F
FAU - Kietzmann, Manfred
AU  - Kietzmann M
FAU - Ohnesorge, Bernhard
AU  - Ohnesorge B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120910
PL  - England
TA  - BMC Vet Res
JT  - BMC veterinary research
JID - 101249759
RN  - 0 (Anti-Asthmatic Agents)
RN  - 2CU6TT9V48 (Leukotriene C4)
RN  - KGZ1SLC28Z (Beclomethasone)
SB  - IM
MH  - Animals
MH  - Anti-Asthmatic Agents/*pharmacology
MH  - Beclomethasone/*pharmacology
MH  - Bronchoconstriction/*drug effects
MH  - Female
MH  - *Horses
MH  - Leukotriene C4/*pharmacology
MH  - Lung/*drug effects/physiology
MH  - Male
PMC - PMC3485115
EDAT- 2012/09/12 06:00
MHDA- 2013/03/26 06:00
PMCR- 2012/09/10
CRDT- 2012/09/12 06:00
PHST- 2011/11/29 00:00 [received]
PHST- 2012/08/13 00:00 [accepted]
PHST- 2012/09/12 06:00 [entrez]
PHST- 2012/09/12 06:00 [pubmed]
PHST- 2013/03/26 06:00 [medline]
PHST- 2012/09/10 00:00 [pmc-release]
AID - 1746-6148-8-160 [pii]
AID - 10.1186/1746-6148-8-160 [doi]
PST - epublish
SO  - BMC Vet Res. 2012 Sep 10;8:160. doi: 10.1186/1746-6148-8-160.