PMID- 28555112
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 8
DP  - 2017
TI  - Caveolin-1: Functional Insights into Its Role in Muscarine- and Serotonin-Induced 
      Smooth Muscle Constriction in Murine Airways.
PG  - 295
LID - 10.3389/fphys.2017.00295 [doi]
LID - 295
AB  - An increased bronchoconstrictor response is a hallmark in the progression of 
      obstructive airway diseases. Acetylcholine and 5-hydroxytryptamine (5-HT, 
      serotonin) are the major bronchoconstrictors. There is evidence that both 
      cholinergic and serotonergic signaling in airway smooth muscle (ASM) involve 
      caveolae. We hypothesized that caveolin-1 (cav-1), a structural protein of 
      caveolae, plays an important regulatory role in ASM contraction. We analyzed 
      airway contraction in different tracheal segments and extra- and intrapulmonary 
      bronchi in cav-1 deficient (cav-1-/-) and wild-type mice using organ bath 
      recordings and videomorphometry of methyl-beta-cyclodextrin (MCD) treated and 
      non-treated precision-cut lung slices (PCLS). The presence of caveolae was 
      investigated by electron microscopy. Receptor subtypes driving 5-HT-responses 
      were studied by RT-PCR and videomorphometry after pharmacological inhibition with 
      ketanserin. Cav-1 was present in tracheal epithelium and ASM. Muscarine induced a 
      dose dependent contraction in all airway segments. A significantly higher Emax 
      was observed in the caudal trachea. Although, caveolae abundancy was largely 
      reduced in cav-1-/- mice, muscarine-induced airway contraction was maintained, 
      albeit at diminished potency in the middle trachea, in the caudal trachea and in 
      the bronchus without changes in the maximum efficacy. MCD-treatment of PLCS from 
      cav-1-/- mice reduced cholinergic constriction by about 50%, indicating that 
      cholesterol-rich plasma domains account for a substantial portion of the 
      muscarine-induced bronchoconstriction. Notably, cav-1-deficiency fully abrogated 
      5-HT-induced contraction of extrapulmonary airways. In contrast, 5-HT-induced 
      bronchoconstriction was fully maintained in cav-1-deficient intrapulmonary 
      bronchi, but desensitization upon repetitive stimulation was enhanced. RT-PCR 
      analysis revealed 5-HT1B, 5-HT2A, 5-HT6, and 5-HT7 receptors as the most 
      prevalent subtypes in the airways. The 5-HT-induced-constriction in PCLS could be 
      antagonized by ketanserin, a 5-HT2A receptor inhibitor. In conclusion, the role 
      of cav-1, caveolae, and cholesterol-rich plasma domains in regulation of airway 
      tone are highly agonist-specific and dependent on airway level. Cav-1 is 
      indispensable for serotonergic contraction of extrapulmonary airways and 
      modulates cholinergic constriction of the trachea and main bronchus. Thus, 
      cav-1/caveolae shall be considered in settings such as bronchial hyperreactivity 
      in common airway diseases and might provide an opportunity for modulation of the 
      constrictor response.
FAU - Keshavarz, Maryam
AU  - Keshavarz M
AD  - Institute of Anatomy and Cell Biology, Justus-Liebig-University GiessenGiessen, 
      Germany.
FAU - Schwarz, Heike
AU  - Schwarz H
AD  - Leibniz Institute for Prevention Research and Epidemiology - BIPSBremen, Germany.
FAU - Hartmann, Petra
AU  - Hartmann P
AD  - Institute of Anatomy and Cell Biology, Justus-Liebig-University GiessenGiessen, 
      Germany.
FAU - Wiegand, Silke
AU  - Wiegand S
AD  - Institute of Anatomy and Cell Biology, Justus-Liebig-University GiessenGiessen, 
      Germany.
FAU - Skill, Melanie
AU  - Skill M
AD  - Institute of Anatomy and Cell Biology, Justus-Liebig-University GiessenGiessen, 
      Germany.
FAU - Althaus, Mike
AU  - Althaus M
AD  - Institute of Anatomy and Cell Biology, School of Medicine, Saarland 
      UniversityHomburg/Saar, Germany.
FAU - Kummer, Wolfgang
AU  - Kummer W
AD  - Institute of Anatomy and Cell Biology, Justus-Liebig-University GiessenGiessen, 
      Germany.
AD  - German Center for Lung Research (DZL)Germany.
FAU - Krasteva-Christ, Gabriela
AU  - Krasteva-Christ G
AD  - Institute of Anatomy and Cell Biology, School of Medicine, Saarland 
      UniversityHomburg/Saar, Germany.
AD  - German Center for Lung Research (DZL)Germany.
LA  - eng
PT  - Journal Article
DEP - 20170515
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC5430063
OTO - NOTNLM
OT  - 5-HT
OT  - airway smooth muscle
OT  - bronchus
OT  - caveolin-1
OT  - contraction
OT  - muscarine
EDAT- 2017/05/31 06:00
MHDA- 2017/05/31 06:01
PMCR- 2017/05/15
CRDT- 2017/05/31 06:00
PHST- 2017/02/21 00:00 [received]
PHST- 2017/04/24 00:00 [accepted]
PHST- 2017/05/31 06:00 [entrez]
PHST- 2017/05/31 06:00 [pubmed]
PHST- 2017/05/31 06:01 [medline]
PHST- 2017/05/15 00:00 [pmc-release]
AID - 10.3389/fphys.2017.00295 [doi]
PST - epublish
SO  - Front Physiol. 2017 May 15;8:295. doi: 10.3389/fphys.2017.00295. eCollection 
      2017.