Premium
Gq‐coupled vasopressor receptors are essential mechanosensitive components for the myogenic vasoconstriction
Author(s) -
Schnitzler Michael Mederos y,
Storch Ursula,
Meibers Simone,
Essin Kirill,
Breit Andreas,
Gollasch Maik,
Gudermann Thomas
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.737.5
Subject(s) - receptor , vascular smooth muscle , agonist , endocrinology , angiotensin ii , microbiology and biotechnology , medicine , vasoconstriction , mechanosensitive channels , chemistry , trpc , stimulation , gq alpha subunit , g protein coupled receptor , biology , ion channel , transient receptor potential channel , smooth muscle
The distal steps of the signalling cascade leading to myogenic constriction in vascular smooth muscle cells have been well investigated, while sensing and the proximal steps are enigmatic. Here we show that mechanical membrane stretch and osmotic cell swelling agonist‐independently activate G q ‐coupled receptors, and subsequently TRPC channels. Using BRET, β‐arrestin was shown to be recruited to the receptor by membrane stretch in a way similar to that seen on agonist stimulation. Simultaneous agonist and mechanical stimulation led to a leftward shift of the angiotensin II‐concentration response curve. Receptor activation and the subsequent signalling cascade could be blocked at different levels. We show that G q ‐coupled receptors like AT 1 angiotensin II and V 1A vasopressin receptors are activated by membrane stretch dependent on their receptor density. Elevated expression levels of AT 1 receptors in A7r5 cells, as well as high endogenous expression levels in renal vascular smooth muscle cells were sufficient for mechanosensivity. In rat cerebral and mouse renal arteries, myogenic tone was profoundly diminished by incubation with the AT 1 receptor inverse agonist losartan. Thus, G q ‐coupled receptors are important components of the mechanosensory complex in vascular smooth muscle cells.