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Hot, Heat and Stretch All Contribute to the Enhanced Ca 2+ Signaling in Pulmonary Arterial Hypertension
Author(s) -
Song Shanshan,
Yamamura Aya,
Yamamura Hisao,
Babicheva Aleksandra,
Tang Haiyang,
Ayon Ramon J,
McDermott Kimberly M.,
Sun Xutong,
Black Stephen M.,
Makino Ayako,
Yuan Jason X.J.
Publication year - 2016
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.30.1_supplement.774.10
Subject(s) - capsaicin , trpv1 , chemistry , trpm8 , transient receptor potential channel , pharmacology , downregulation and upregulation , medicine , extracellular , endocrinology , anesthesia , receptor , biochemistry , gene
Capsaicin is an active component of chili peppers and an irritant for mammals and humans. The dried chili pepper is a commonly consumed food ingredient and capsaicin is a potent inhibitor of substance P which is associated with inflammation and pain. Capsaicin is an important pain relief drug for patients with osteoarthritis pain, cancer‐associated pain and diabetic neuropathy‐mediated pain. In this study, we studied the effect of capsaicin on human pulmonary arterial smooth muscle cells (PASMC) from normal subjects and patients with idiopathic pulmonary arterial hypertension (IPAH). Our observations show that TRPV1, the capsaicin receptor and a transient receptor potential (TRP) cation channel in the TRP vanillioid family, is upregulated while capsaicin‐induced increase in cytosolic free Ca 2+ concentration ([Ca 2+ ] cyt ) is enhanced in IPAH‐PASMC compared with normal PASMC. TRPV1 is not only activated by capsaicin, but also activated by heat (>43°C or 102°F), acid (H +) , and osmotic pressure changes. Indeed, the increasing temperature from 24°C to 43°C, or decreasing extracellular pH value from 7.4 to 5.0, both significantly enhanced capsaicin‐induced increases in [Ca 2+ ] cyt . The heat‐(from 24°C to 43°C) and acidic pH (5.0)‐mediated enhancement of capsaicin‐induced increases in [Ca 2+ ] cyt is greater in IPAH‐PASMC than in normal PASMC, potentially because of upregulated TRPV1 channels. These data indicate that upregulated TRPV1 expression and subsequent enhancement of capsaicin‐, heat‐ and acid‐mediated increases in [Ca 2+ ] cyt in PASMC may play an important role in the development and progression of pulmonary arterial hypertension by inducing sustained pulmonary vasoconstriction and pulmonary vascular remodeling, while blockers of TRPV1 (e.g., capsazepine, yohimbine and cinnamides) can potentially be new therapies for PAH.