The role of ion channels and protein kinase C activation in the stimulation of complement protein synthesis.
Monocyte C2 synthesis is stimulated by antigen-antibody complexes (IC), carbamylcholine (C-Ch), phenylephrine (PE) and gamma-interferon. Tetrodotoxin or nifedipine abrogated the effects of IC, C-Ch and PE but did not influence the effect of gamma-interferon on C2 synthesis. Thus stimulation of C2 synthesis by IC, C-Ch and PE is dependent upon activation of Na+/K+ and Ca2+ channels, whereas gamma-interferon operates independently of these ion channels. Calcium channel agonists (CG28392 and BK8644) stimulated C2 synthesis, and this effect was prevented by nifedipine but not by tetrodotoxin. Thus Na+/K+ channels are activated prior to Ca2+ channels. Stimulation of C2 synthesis occurred when phospholipase C or phorbol myristate acetate (PMA) were added to the monocyte cultures, suggesting that PI cycle turnover and protein kinase-C (PK-C) activation are involved in the stimulation of C2 synthesis in monocytes. PMA, an activator of PK-C, stimulated the synthesis of C2, C3, B, P and C1-inhibitor approximately two-fold. In contrast gamma-interferon reduced synthesis of C3 and P by 44% and 22% respectively, and stimulated C1-inhibitor synthesis twelve-fold. These data suggest that the action of gamma-interferon complement synthesis is, at least partially, independent of PK-C activation. The effects of IC, C-Ch, PE, PI, CG28392, BK8644 and gamma-interferon were inhibited by trifluoperazine implying that calmodulin and/or other calcium binding proteins play a role in the modulation of complement protein production.
D002120:Calcium Channel Agonists / Q000494:pharmacology; D003175:Complement C2 / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002120:Calcium Channel Agonists; D003175:Complement C2; D007473:Ion Channels; D014268:Trifluoperazine; D013779:Tetrodotoxin; D007371:Interferon-gamma; D012964:Sodium; D011493:Protein Kinase C; D009543:Nifedipine