Opposite effects of interleukin-2 (IL-2) and interferon gamma (IFN gamma) on rat atria contractility.
We have recently shown that interleukin 2 (IL-2) can increase the contractile strength or rat atrial muscle through the activation of phospholipases and protein kinase C. The results of this study confirm that the reaction of IL-2 with rat atria involves protein kinase C and not the Ca(++)-calmodulin dependent kinases. Phorbol 12-myristate 13-acetate (PMA), a tumor promoter that activates protein kinase C directly (bypassing the phosphoinositide turnover step), has effects that are similar to those of IL-2 on atrial contractility. Furthermore, preincubation of the tissue with PMA prevents the IL-2 effect, suggesting that the kinases activated by the tumor promoter and IL-2 share a common substrate. This effect of IL-2 on atrial contractility opposes the cholinomimetic inhibitory action of IFN gamma. Thus, preincubation of cardiac tissue with IL-2 or PMA eliminates the effects of IFN gamma and viceversa. Apparently, the inhibitory action of IL-2 on IFN gamma involves an impaired response or atria to cholinergic activation, as IL-2 shifts to the right the dose response curve of the tissue to the cholinergic muscarinic agonist carbachol. Protein kinase C is also necessary for the occurrence of the IL-2-IFN gamma interference. The results of this study suggest that, during an inflammatory reaction in the heart, the balance of the two lymphokines can determine changes in the response of the tissue to autonomous nervous system agonists or to the cytokines that mimic the effects of these neurotransmitters.
de Bracco
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MM
Instituto de Investigaciones Hematológicas (IIHEMA), Academia Nacional de Medicina, Buenos Aires, Argentina.
Borda
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ES
Sterin-Borda
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D000818:Animals; D002217:Carbachol / Q000008:administration & dosage; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010740:Phospholipases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D007376:Interleukin-2; D007371:Interferon-gamma; D002217:Carbachol; D011493:Protein Kinase C; D010740:Phospholipases