Positive inotropic effect of interleukin-2. Role of phospholipases and protein kinase C.
Recently, we have shown that soluble factors released by human lymphocytes after lectin stimulation could increase the contractile tension of rat atria "in vitro" and that interleukin-2 (IL-2) could be part of this reaction. The effect of IL-2 was potentiated by the Ca2+ ionophore A23187 or free arachidonic acid (AA). In this study we demonstrate that the action of IL-2 can be prevented by pre-incubation of the heart tissue with monoclonal anti-IL-2 receptor (anti-p55), suggesting that binding to the IL-2 receptor is necessary for the induction of the biologic effect. In the presence of A23187 or AA, the effect of the synthetic diacylglyceride oleoyl-acetyl-glycerol (OAG) was similar to that of IL-2. Elimination of phospholipase C activity by pre-incubation of the atria with 2-nitro-carboxyphenyl,N,N'-diphenylcarbamate (NCDC) abrogated the effects of IL-2 in the presence of A23187 or AA, but was ineffective when OAG + A23187 or OAG + AA was used. Inhibition of atrial phospholipase A2 activity with p-bromo-phenacylbromide (BPB) blocked the response of atria to either IL-2 + A23187 or OAG + A23187 but was not effective when AA was used as second signal (IL-2 + AA or OAG + AA). Both the OAG and the IL-2 positive inotropic effects could be prevented by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H7) but were poorly inhibited by N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), an inhibitor of the cyclic nucleotide-dependent protein kinases.(ABSTRACT TRUNCATED AT 250 WORDS)
de Bracco
M M
MM
Instituto de Investigaciones Hematolögicas. Academia Nacional de Medicina, Buenos Aires, Argentina.
Fink
S B
SB
Finiasz
M R
MR
Borda
E S
ES
Sterin-Borda
L
L
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology*
D001095:Arachidonic Acids; D007376:Interleukin-2; D047428:Protein Kinase Inhibitors; D015375:Receptors, Interleukin-2; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D011494:Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases