AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 282: H1855-H1862, 2002; doi:10.1152/ajpheart.00747.2001
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Vol. 282, Issue 5, H1855-H1862, May 2002

Calcium- and superoxide anion-mediated mitogenic action of substance P on cardiac fibroblasts

C. Kumaran and K. Shivakumar

Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India 695 011

Substance P is released from nerve endings in the heart under pathological conditions like ischemia, but its action on cardiac cells has not been investigated. This study tested the hypothesis that substance P is mitogenic to adult cardiac fibroblasts and delineated the underlying mechanism(s). Substance P, acting via neurokinin-1 (NK-1) receptors, stimulated cellular hyperplasia over a range of 1-10 µmol/l. It elicited no change in net collagen production, total protein synthesis, or cell protein content but increased 45Ca uptake and superoxide generation. EGTA, N-acetyl-cysteine, and superoxide dismutase attenuated the hyperplastic response to substance P. A combination of substance P and EGTA enhanced superoxide generation without an increase in DNA synthesis, showing that an increase in superoxide production does not result in hyperplasia when extracellular Ca2+ is chelated. Together, the data suggest that substance P may activate, via NK-1 receptors, a hyperplastic but not hypertrophic response in adult cardiac fibroblasts and that alterations in redox state and Ca2+ homeostasis may act in concert to mediate its mitogenic action.

peptidergic; neural pathway; calcium signaling; oxidant signaling; hyperplasia


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