Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 microM), added twice daily, inhibited proliferation but 8 bromo cyclic GMP (30 microM) had no effect. Two other stimuli known to increase PAEC cyclic GMP content by stimulating particulate and soluble guanylate cyclase respectively, atriopeptin II (10 nM) and sodium nitroprusside (1 microM), were also without effect on proliferation. 3 Two agents known to inhibit soluble guanylate cyclase and lower intercellular cyclic GMP content, haemoglobin (10 microM) and methylene blue (10 microM), each inhibited proliferation of PAEC. 4 The inhibitory effect of haemoglobin (10 microM) 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 nM), 8 bromo cyclic GMP (30 microM) or sodium nitroprusside (1 microM). The inhibitory effect of methylene blue (10 microM) was not reversed by these agents. 5 Phorbol 12-myristate 13-acetate (PMA, 0.1 nM-1 microM), which activates protein kinase C, inhibited proliferation in a concentration-dependent manner. No early stimulation of proliferation was seen with PMA. The inactive isomer, 4 alpha-phorbol 12,13-didecanoate (0.3 microM), 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 microM) or butylated hydroxytoluene (30 microM). The antiproliferative actions of paraquat (10 microM), an agent which generates free radicals intracellularly, was, in contrast, inhibited by vitamin E or butylated hydroxytoluene. Furthermore, neither dibutyryl cyclic AMP (30 microM) nor 8 bromo cyclic GMP (30 microM) 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.
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PMID:Effects of cyclic nucleotides and phorbol myristate acetate on proliferation of pig aortic endothelial cells. 164 54

Cyclic nucleotide metabolism was examined in rat distal colonic epithelial cells with different proliferative activities. Lower crypt cells had DNA synthetic rates 7-10-fold higher than surface cells. Without a phosphodiesterase inhibitor proliferative cells had reduced basal cyclic AMP-, cyclic GMP-, and cyclic AMP-dependent protein kinase activity ratios, as well as blunted cyclic AMP responses to prostaglandin E2 and vasoactive intestinal peptide compared to superficial cells. In the presence of 3-isobutyl-1-methylxanthine, basal cyclic AMP and responses to prostaglandin E2 and vasoactive intestinal peptide of proliferative cells exceeded values in superficial cells. This correlated with higher membrane adenylate cyclase activity in the proliferative cells. By contrast, particulate and soluble guanylate cyclase activities of superficial cells were higher than in proliferative cells. The apparent high Km soluble and particulate cyclic AMP and cyclic GMP phosphodiesterase activities of proliferative cells were 4-7-fold higher than those in superficial cells. Moreover, the apparent low Km soluble activity was absent in superficial cells. Thus, an altered rate of nucleotide degradation may mediate reduced cyclic AMP and cyclic GMP in proliferative versus superficial cells. Dibutyryl cyclic AMP, prostaglandin E2 or vasoactive intestinal peptide inhibited [3H]thymidine incorporation into DNA of colonic segments. Thus, reduced cyclic AMP in lower crypt cells may be a determinant of their greater proliferative activity.
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PMID:Cyclic nucleotide metabolism in rat colonic epithelial cells with different proliferative activities. 616 89

The effects of cyclic nucleotides and phorbol ester on Ca2+ efflux from cultured bovine adrenal chromaffin cells were examined. Dibutyryl cyclic AMP (DB-cAMP), forskolin (an activator of adenylate cyclase), dibutyryl cyclic GMP (DB-cGMP) and nitroprusside (an activator of guanylate cyclase) all stimulated 45Ca2+ efflux from the cells preloaded with 45Ca2+. These agents did not increase the intracellular free Ca2+ ([Ca2+]i) level. On the contrary, phorbol 12-myristate 13-acetate (PMA; an activator of protein kinase C) did not affect the efflux of 45Ca2+, but inhibited the increase in 45Ca2+ efflux caused by DB-cAMP, forskolin, DB-cGMP or nitroprusside. The 45Ca2+ effluxes stimulated by cyclic nucleotides, forskolin and nitroprusside were inhibited by deprivation of extracellular Na+ ([Na+]o). These results suggest that both cAMP- and cGMP-dependent protein kinases are involved in the stimulatory mechanism of [Na+]o dependent Ca2+ efflux, probably through acceleration of [Na+]o/[Ca2+]i exchange and that protein kinase C plays an inhibitory role in this mechanism.
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PMID:Regulations by cyclic nucleotides and phorbol ester of calcium efflux from cultured bovine adrenal chromaffin cells. 767 26

1. Forskolin, an activator of adenylate cyclase, potentiated the relaxing response to isoproterenol in rabbit aortic rings precontracted by phenylephrine (PE). 2. The potentiating effect of forskolin was inhibited by propranolol, a beta-adrenoceptor inhibitor, but not by methylene blue, a guanylate cyclase inhibitor. 3. The relaxing response to terbutaline, a beta 2-adrenoceptor agonist, but not lower concentrations of dobutamine, a beta 1-adrenoceptor agonist, also was potentiated by forskolin. Forskolin, however, potentiated the relaxing response to high concentrations of dobutamine, which activates both beta 1- and beta 2-adrenoceptors. 4. Yohimbine, an alpha 2-adrenoceptor inhibitor, glyburide, an ATP-sensitive K+ channel inhibitor, iberiotoxin, a Ca(2+)-activated K+ channel inhibitor, or endothelium-removal failed to affect the potentiating effect of forskolin. 5. Dibutyryl cyclic AMP (cAmp) also potentiated the relaxing response to terbutaline. 6. These results suggest that in rabbit aortic rings forskolin causes the apparent potentiation of isoproterenol-induced relaxation by mainly affecting the relaxing response due to the activation of beta 2-adrenoceptors by the forskolin-induced increase in the level of cAMP.
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PMID:Potentiation of the relaxing action of isoproterenol by forskolin in rabbit aortic rings: the involvement of beta 2-adrenoceptors. 918 14