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Effects of cyclic nucleotides and phorbol myristate acetate on proliferation of pig aortic endothelial cells
Author(s) -
Moodie Shonna Alexandra,
Martin William
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12139.x
Subject(s) - sodium nitroprusside , protein kinase c , phorbol , chemistry , cyclic nucleotide , methylene blue , protein kinase a , endocrinology , stimulation , medicine , cyclic gmp , biochemistry , cell growth , cyclase , nucleotide , kinase , nitric oxide , biology , receptor , enzyme , photocatalysis , gene , catalysis
1 The role of cyclic nucleotides and protein kinase C in controlling proliferation of pig aortic endothelial cells (PAEC) in culture was investigated. 2 Dibutyryl cyclic AMP (30 μ m ), added twice daily, inhibited proliferation but 8 bromo cyclic GMP (30 μ m ) had no effect. Two other stimuli known to increase PAEC cyclic GMP content by stimulating particulate and soluble guanylate cyclase respectively, atriopeptin II (10 n m ) and sodium nitroprusside (1 μ m ), were also without effect on proliferation. 3 Two agents known to inhibit soluble guanylate cyclase and lower intercellular cyclic GMP content, haemoglobin (10 μ m ) and methylene blue (10 μ m ), each inhibited proliferation of PAEC. 4 The inhibitory effect of haemoglobin (10 μ m ) was mediated by inhibition of soluble guanylate cyclase since it was reversed by agents known to increase cyclic GMP content, i.e. atriopeptin II (10 n m ), 8 bromo cyclic GMP (30 μ m ) or sodium nitroprusside (1 μ m ). The inhibitory effect of methylene blue (10 μ m ) was not reversed by these agents. 5 Phorbol 12‐myristate 13‐acetate (PMA, 0.1 n m –1 μ m ), which activates protein kinase C, inhibited proliferation in a concentration‐dependent manner. No early stimulation of proliferation was seen wtih PMA. The inactive isomer, 4α‐phorbol 12, 13‐didecanoate (0.3 μ m ), lacked the ability of PMA to inhibit proliferation of PAEC. 6 PMA‐induced inhibition of proliferation appeared not to be due to stimulated production of destructive oxygen‐derived free radicals since it was unaffected by the radical scavengers, vitamin E (30 μ m ) or butylated hydroxytoluene (30 μ m ). The antiproliferative actions of paraquat (10 μ m ), an agent which generates free radicals intracellularly, was, in contrast, inhibited by vitamin E or butylated hydroxytoluene. Furthermore, neither dibutyryl cyclic AMP (30 μ m ) nor 8 bromo cyclic GMP (30 μ m ) had any effect on the ability of PMA to inhibit proliferation. 7 This study suggests that cyclic AMP, cyclic GMP and protein kinase C play a role in controlling the proliferation of PAEC.