Premium
Protein Tyrosine Phosphatase 1B is a negative regulator of alpha‐adrenergic vasoconstriction in mouse aorta
Author(s) -
Chantemele Eric Belin,
Ketsawatsomkron Pimonrat,
Marrero Mario,
Stepp David
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.744.8
Subject(s) - vasoconstriction , electrical impedance myography , contraction (grammar) , endocrinology , medicine , protein tyrosine phosphatase , vascular smooth muscle , calphostin c , chemistry , phenylephrine , mapk/erk pathway , protein kinase c , signal transduction , vasodilation , receptor , blood pressure , biochemistry , smooth muscle
Protein tyrosine phosphatases, such as 1B (PTP1B) act as counter‐regulators of tyrosine kinases to modulate signal transduction. While tyrosine kinases are involved in vascular function, effects of PTP1B on vascular reactivity are unknown. We hypothesized that PTP1B modulates aortic contraction. Aortic contraction was examined by myography using PTP1B knockout (KO) mice and Balb/C controls (CON). PTP1B deletion reduced blood pressure (CON: 112±2 vs KO: 106±2mmHg, p<0.05). Phenylephrine (PE)‐induced maximum contraction was reduced in KO mice (CON: 96.3±12 vs KO: 57.7±9% of KCl, p<0.05) with no effect on KCl or serotonin (5HT)‐mediated contraction. To analyze the mechanisms involved, contraction to PE, 5HT and KCl were conducted in the presence of PKC (Calphostin C), ERK1/2 (PD98059) and ROK inhibitors (Y27632). Inhibitors had no effect on the 5HT, KCL‐mediated contraction suggesting lack of dependence on PKC, MAPK and ROK. PKC inhibition reduced similarly contraction to PE in CON and KO mice. The inhibitory effects of PD98059 (CON: 12.6±16 vs KO: 55.7±11%, p<0.05) and Y27632 (CON: 48.6±9 vs KO: 70.2±6%, p<0.05) were higher in KO mice arguing for a higher involvement of MAPK and ROK in PE‐induced contraction in KO mice. These data identify PTP1B as a novel negative regulator of adrenergic contraction in vascular smooth muscle via MAPK and ROK signaling and may explain reduced blood pressure in PTP1B KO mice.