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Up‐regulation of RGS2 Mediate IL‐1beta‐Induced Decrease in Muscle Contraction in Response to NPR‐C activation in Tenia Coli
Author(s) -
Mahavadi Sunila,
Khaleduzzaman Mohammed,
Grider John R,
Murthy Karnam S
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.983.3
Subject(s) - chemistry , contraction (grammar) , medicine , endocrinology , muscle contraction , receptor , biochemistry , biology
The proinflammatory cytokine, interleukine‐1β (IL‐1β), plays an important role in inflammation‐induced changes in smooth muscle contraction. IL‐1β inhibits acetylcholine release and muscle contraction in response to Gq‐coupled m3 receptor activation. Our previous studies have shown that the single‐transmembrane natriuretic peptide receptor, NPR‐C is coupled to Gi to stimulation of phosphoinositide (PI) hydrolysis via Gβγ i and muscle contraction. AIM To characterize the effect of IL‐1β on contraction in response to NPR‐C activation. METHODS Rabbit tenia coli were cultured in DMEM‐10 in the presence or absence of IL‐1β for 48 h. Muscle cells isolated from these strips were used for measurement of NPR‐C binding, PLC‐β3 and RGS2 expression, and cANP‐induced PI hydrolysis and muscle contraction. RESULTS Pre‐incubation with IL‐1β had no effect on NPR‐C binding or PLC‐β3 expression, but significantly inhibited cANP‐induced PI hydrolysis and muscle contraction. IL‐1β caused a 3‐4 fold‐increase in RGS2, a GTPase‐activating protein that accelerates inactivation of Gαi‐GTP, implying that the decrease in PI hydrolysis and contraction were mediated by increased deactivation of Gαi and formation of Gαβ γtrimer. CONCLUSION Inhibition of cANP‐induced contraction by IL‐1β reflects inhibition of PI hydrolysis resulting from up‐regulation of RGS2 and rapid inactivation of Gαi and inhibition of Gβγ i‐mediated PI hydrolysis.