title: Positive inotropic effect of interleukin-2. Role of phospholipases and protein kinase C.
abstract: 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)
authors.affiliation: Instituto de Investigaciones Hematolögicas. Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: M M
authors.initials: MM
authors.lastname: de Bracco
authors.forename: S B
authors.initials: SB
authors.lastname: Fink
authors.forename: M R
authors.initials: MR
authors.lastname: Finiasz
authors.forename: E S
authors.initials: ES
authors.lastname: Borda
authors.forename: L
authors.initials: L
authors.lastname: Sterin-Borda
mesh_terms: 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*
chemical_list: 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