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Contraction of rat vena cava by endothelin‐1 is dependent on phospholipase‐Cβ, but independent of IP 3 receptor activation
Author(s) -
Tykocki Nathan R.,
Wu BinXi,
Jackson William F.,
Watts Stephanie W.
Publication year - 2012
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.26.1_supplement.1049.3
Subject(s) - phospholipase c , contraction (grammar) , medicine , phosphatidylinositol , endocrinology , endothelin 1 , receptor , inferior vena cava , diacylglycerol kinase , chemistry , biology , signal transduction , protein kinase c , biochemistry
In vascular smooth muscle, inositol 1,4,5‐trisphosphate (IP 3 ) regulates excitation‐contraction coupling by activating the release of sarcoplasmic Ca 2+ stores. IP 3 is produced through the activity of phospholipase Cβ (PLCβ), which cleaves phosphatidylinositol into diacylglycerol (DAG) and IP 3 . While the vasoconstrictor ET‐1 activates PLCβ and increases IP 3 formation in arteries, it is unclear if this is so in veins. We hypothesized that contraction to ET‐1 in rat aorta (RA) and vena cava (RVC) depends upon IP 3 ‐mediated Ca 2+ release. To test if PLCβ was activated by ET‐1, isometric contraction was measured in RA and RVC rings exposed to vehicle, the PLCβ inhibitor U‐73122 or its inactive analog U‐ 73343 (1 μM), or the IP 3 receptor antagonist 2‐APB (100 μM). While U‐73343 did not significantly inhibit contraction to ET‐1, U‐73122 significantly reduced maximum contraction to ET‐1 in RA (86±6% of control) and RVC (49±11% of control). Contrary to our hypothesis, 2‐APB significantly reduced maximum contraction to ET‐1 only in RA (55±4%) and not RVC (82±8%). These data were supported by Western blot analysis, showing 63.1 times more IP 3 R‐1 and 12.6 times more IP 3 R‐2 protein in RA than RVC, as measured by densitometry. These findings suggest that ET‐1 does activate PLCβ in RA and RVC, but only contraction to ET‐1 in RA is regulated by IP 3 . Rather, DAG and not IP 3 may regulate contraction to ET‐1 in RVC. Supported by NIH P01HL70687.