Integration of signalling in smooth muscle caveolae
Författare
Summary, in English
Ca2+-sensitization is a contractile process depending on inhibition of myosin phosphatase activity. Here I test whether protein kinase C and Rho-associated kinase-mediated Ca2+ sensitization depends on caveolae using gene disrupted (KO) mice. While the process of Ca2+ sensitization was unaffected by lack of caveolae in the intestine, α1-adrenergic and protein kinase C-mediated arterial contraction was increased. Arteries lacking caveolae weighed more per unit length, suggesting growth
of the arterial wall. I go on to demonstrate that small resistance arteries from KO mice are remodelled, and that these and other changes counterbalance an excessive NO production to normalize blood pressure in caveolin-1 deficient mice.
NO production is required for initiating and maintaining penile erection. Surprisingly, nerve-induced relaxation and relaxation in response carbachol and sodium nitroprusside was impaired in caveolae-deficient corpus cavernosum.
In the last two papers, I examine the role of caveolae in detrusor function. Disruption of caveolae using desorption of cholesterol was first shown to impair contraction of human bladder strips in response to muscarinic receptor activation. I then demonstrate that the membrane density of caveolae increases after bladder outlet obstruction in
the rat. The latter effect was due to crowding of the same relative number of caveolin molecules on a smaller relative membrane area.
In conclusion, a considerable body of evidence has been gathered that demonstrate an important and pleiotropic physiological and pathophysiological role of caveolae in smooth muscle
Avdelning/ar
Publiceringsår
2010
Språk
Engelska
Publikation/Tidskrift/Serie
Lund University Faculty of Medicine Doctoral Dissertation Series
Volym
2010:111
Fulltext
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Dokumenttyp
Doktorsavhandling
Förlag
Department of Experimental Medical Science, Lund Univeristy
Ämne
- Cell and Molecular Biology
Nyckelord
- Caveola
- caveolin
- detrusor
- cavin
- smooth muscle contractility
- remodelling
- NO
- vascular dysfunction
- smooth muscle
- erectile dysfunction
Status
Published
Forskningsgrupp
- Cellular Biomechanics
Handledare
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-86671-27-3
Försvarsdatum
9 december 2010
Försvarstid
09:00
Försvarsplats
Segerfalksalen, Biomedical Center, Sölvegatan 19, Lund
Opponent
- Ralph Peeker (MD)