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Phospholipase Cγ1 is Required for Pressure‐Induced Vasoconstriction of Cerebral Arteries
Author(s) -
Herrera Carlos Eduardo,
Crnich Rachael,
Earley Scott
Publication year - 2009
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.23.1_supplement.613.16
Subject(s) - vasoconstriction , phospholipase c , cerebral arteries , agonist , vascular smooth muscle , diacylglycerol kinase , purinergic receptor , endocrinology , vasodilation , medicine , second messenger system , chemistry , vasoconstrictor agents , biology , signal transduction , receptor , protein kinase c , microbiology and biotechnology , smooth muscle
Phospholipase C (PLC) hydrolyzes the phosphodiester bond of the membrane phospholipid phosphotidylinositol (4,5)‐bisphosphate (PtdIns(4,5)P 2 ) to generate the second messengers diacylglycerol (DAG) and inositol 1,4,5‐trisphosphate (IP 3 ). A number of PLC isoforms are present in vascular smooth muscle cells, including members of the PLCβ, PLCg, and PLCd families. Pharmacological inhibition of PLC activity blocks both pressure‐ and agonist‐induced vasoconstriction. To test the hypothesis that specific PLC isoforms influence discreet vasoconstrictor pathways, we used small interfering RNA (siRNA) to silence PLCγ1 expression in intact cerebral resistance arteries. Expression of PLCγ1 in intact cerebral arteries treated with siRNA was reduced by approximately 70% compared to controls. Arteries treated with PLCγ1 siRNA failed to constrict in response to increases in intraluminal pressure. In contrast, vasoconstriction in response to the purinergic receptor agonist uridine triphoshphate (UTP) did not differ between PLCγ1 siRNA‐treated arteries and controls. These finding demonstrate that PLCγ1 is required to regulate myogenic responsiveness, whereas other PLC isoforms regulate agonist‐induced vasoconstriction. AHA0535226N.