Premium
Platelet‐derived growth factor and angiotensin II cause increases in cytosolic free calcium by different mechanisms in vascular smooth muscle cells
Author(s) -
Roe Michael W.,
Hepler John R.,
Harden T. Kendall,
Herman Brian
Publication year - 1989
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041390115
Subject(s) - cytosol , vascular smooth muscle , angiotensin ii , calcium , microbiology and biotechnology , platelet , platelet derived growth factor , chemistry , growth factor , smooth muscle , endocrinology , medicine , platelet derived growth factor receptor , biology , biochemistry , receptor , enzyme
Platelet‐derived growth factor (PDGF) and angiotensin II (All) are thought to mediate their biological effects in vascular smooth muscle cells (VSMCs) by causing alterations in cytosolic free calcium ([Ca 2+ ] i ). In this study we examine the pathways by which PDGF and All alter [Ca 2 + ] i in VSMCs. Addition of PDGF resulted in a rapid, transient, concentration‐dependent increase in [Ca 2+ ] i ; this rise in [Ca 2 + ] i was blocked completely by preincubation of cells with ethylene glycol‐ bis (β‐aminoethyl ether) N,N,N′,N′‐tetraacetic acid (EGTA) or CoCl 2 , by the voltage‐sensitive Ca 2 + ‐channel antagonists verapamil or nifedipine, by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), or by pertussis toxin. All also caused an increase in [Ca 2 + ] i ; however, All‐stimulated alterations in [Ca 2+ ] i displayed different kinetics compared with those caused by PDGF. Pretreatment of cells with 8‐(diethylamine)‐octyl‐3,4,5‐trimethyoxybenzoate hydrochloride (TMB‐8), almost totally inhibited All‐induced increases in [Ca 2+ ] i . EGTA or CoCl 2 only slightly diminished All‐stimulated increases in [Ca 2+ ] i . Nifedipine, verapamil, TPA, and pertussis toxin pretreatment were without effect on All‐induced increases in [Ca 2+ ] i . PDGF and All both stimulated increases in total inositol phosphate accumulation, although the one‐half maximal concentration (ED 50 ) for alterations in [Ca 2+ ] i and phosphoinisitide hydrolysis differed by a factor of 10 for PDGF (3 × 10 −10 M for Ca 2+ vs. 2.5 × 10 −9 M for phosphoinositide hydrolysis), but they were essentially identical for All (7.5 × 10 −9 M for Ca 2+ vs. 5.0 × 10 −9 M for phosphoinositide hydrolysis). PDGF stimulated mitogenesis (as measured by [ 3 H]‐thymidine incorporation into DNA) in VSMCs with an ED 50 similar to that for PDGF‐induced alterations in phosphoinositide hydrolysis. PDGF‐stimulated mitogenesis was blocked by pretreatment of cells with voltage‐sensitive Ca 2 + channel blockers, TPA, or pertussis toxin. These results suggest that PDGF and All cause alterations in [Ca 2+ ] i in VSMCs by at least quantitatively distinct mechanisms. PDGF binding activates a pertussis‐toxin‐sensitive Ca 2+ influx into cells via voltage‐sensitive Ca 2+ channels (blocked by EGTA, verapamil, and nifedipine), as well as stimulating phosphoinositide hydrolysis leading to release of Ca 2+ from intracellular stores. All‐induced alterations in [Ca 2+ ] i are mainly the result of phosphoinositide hydrolysis and consequent entry of Ca 2+ into the cytoplasm from intracellular stores. Our data also suggest that changes in [Ca 2 + ] i caused by PDGF are required for PDGF‐stimulated mitogenesis.