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Lysosomal Calcium: Impact on Serotonin‐Induced Contractions of Ovine Pulmonary Arteries
Author(s) -
Arnold Amy,
Linklater Lorna,
Widmer Helene,
Rowe Iain,
Cruickshank Stuart
Publication year - 2015
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.29.1_supplement.804.3
Subject(s) - contraction (grammar) , extracellular , nimodipine , endocrinology , serotonin , chemistry , medicine , calcium , electrical impedance myography , pulmonary artery , intracellular , vascular smooth muscle , muscle contraction , acetylcholine , smooth muscle , vasodilation , biochemistry , receptor
Mobilisation of intracellular Ca 2+ from lysosomes is involved in smooth muscle contraction in response to several agonists but serotonin (5‐HT) has not been examined. Given the proposed role of 5‐HT in pulmonary arterial hypertension, this study aimed to investigate the role of lysosomal Ca 2+ stores in pulmonary artery (PA) smooth muscle 5‐HT responses. Responses of endothelium‐denuded ovine PAs were measured using myography. 5‐HT cumulative concentration response curves (CCRCs) were investigated in Ca 2+ ‐free medium and with nimodipine (a lysosomal Ca 2+ channel blocker). Contractions are normalised to 80mM KCl responses and expressed as mean ± S.E.M. PAs showed dose‐dependent contractions to 5‐HT. Fourth order PAs were more responsive than third order; maximal contractions were significantly higher (P<0.05). Responses to 5‐HT were reduced in the absence of extracellular Ca 2+ (statistically significant at [5‐HT] of 30μM and 100μM (P<0.05)). Maximal contraction: Ca 2+ ‐free medium 174±20%KCl (n=5); Ca 2+ ‐containing medium 282±17%KCl (n=5). PAs in Ca 2+ ‐free medium containing nimodipine displayed reduced contractions to 5‐HT compared to control (statistically significant (P<0.05) at [5‐HT] of 10μM, 30μM and 100μM). Nimodipine reduced maximal contraction at 30μM 5‐HT by 56±4%: nimodipine‐exposed PAs 73±7%KCl (n=5); control 174±20%KCl (n=5). Anatomical order in ovine PAs is an important factor in 5‐HT responsiveness. Results also suggest both extracellular Ca 2+ and mobilisation of Ca 2+ from intracellular lysosomal stores play a significant role in 5‐HT‐mediated contraction of ovine PAs. Research supported by Institute for Health & Wellbeing Research, Robert Gordon University.