Manidipine regulates the transcription of cytokine genes.
Manidipine, a Ca(2+)-channel blocker, at concentrations that lower elevated blood pressure, modulates the transcription rates of cytokine genes in the mesangial cells of humans that had been stimulated with platelet-derived growth factor BB isomer; although the transcription for mRNA of interleukin 1 beta and granulocyte/monocyte colony-stimulating factor was inhibited, the transcription of mRNA for interleukin 6 was enhanced. Additionally, the induction of c-fos, c-jun, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase transcription was inhibited by manidipine. We conclude that manidipine, at nanomolar concentrations, is efficacious in modulating gene transcriptions that are involved in proinflammatory changes of mesangial cells. Thus, manidipine, at pharmacological concentrations that are one to two orders of magnitude lower than those required for inhibition of agonist- or depolarization (K+)-induced vasoconstriction, causes changes in the activity of the genes that code for inflammatory mediators.
Roth
M
M
Department of Medicine, University of Freiburg, Federal Republic of Germany.
Keul
R
R
Emmons
L R
LR
Hörl
W H
WH
Block
L H
LH
D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000235:genetics*; D004247:DNA / Q000096:biosynthesis; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D016758:Genes, jun; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D009578:Nitrobenzenes; D010879:Piperazines; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
D002121:Calcium Channel Blockers; D016207:Cytokines; D004095:Dihydropyridines; D007375:Interleukin-1; D015850:Interleukin-6; D009578:Nitrobenzenes; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C054218:manidipine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D006903:Hydroxymethylglutaryl CoA Reductases; D011493:Protein Kinase C; D002118:Calcium