{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:35:14Z","timestamp":1773290114476,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":608,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Deficiency in nitric oxide (NO) is a major factor leading to deterioration and progression of certain glomerular diseases. Agents enhancing NO availability and potentiality are renoprotective. Irsogladine maleate (IM), an anti\u2010ulcer drug, is reported to improve gastric blood flow via NO\u2010dependent mechanisms. We, therefore, asked whether and how IM interacted with NO on glomerular mesangial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Mesangial cells were exposed to IM and NO donors. Activation of cAMP signalling pathways was assessed by intracellular cAMP, phosphorylation of VASP, activation of the cAMP response element (CRE) and expression of CRE\u2010regulated proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>IM alone did not affect cell proliferation. However, it greatly enhanced the growth\u2010inhibitory effect of NO donor S\u2010nitroso\u2010N\u2010acetylpenicillamine (SNAP). IM acted synergistically with NO on suppression of mitogen\u2010activated protein kinase activation, induction of gap junction protein connexin43, increase of intracellular cAMP, and phosphorylation of VASP. With the use of the CRE\u2010SEAP\u2010based reporting system, IM and SNAP cooperatively activated cAMP response elements (CRE). A similar activation of cAMP was induced by IM with two different NO donors, the sGC activator Bay 41\u20102272 and the cGMP analogue 8\u2010bromo\u2010cGMP. The effects of SNAP and IM on cAMP activation were mimicked by phosphodiesterase 3 (PDE3) and PDE4 inhibitors. In addition, IM markedly augmented cytokine\u2010induced expression of iNOS, production of NO and activation of CRE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and implications:<\/jats:title><jats:p>The effects of NO were greatly potentiated by IM through synergistic activation of cAMP pathway. Combined therapy with IM and NO may be developed for certain renal diseases.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2007) <jats:bold>151<\/jats:bold>, 457\u2013466; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707255\">10.1038\/sj.bjp.0707255<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0707255","type":"journal-article","created":{"date-parts":[[2007,4,16]],"date-time":"2007-04-16T10:55:27Z","timestamp":1176720927000},"page":"457-466","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Irsogladine maleate potentiates the effects of nitric oxide on activation of cAMP signalling pathways and suppression of mesangial cell 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