RESUMO
Although there are several reports on the regulation of neuronal and skeletal muscle voltage-sensitive calcium channels by IGF1, the effects of short-term IGF1 exposure on cardiac Ca2+ channels have not been described. We measured the activity of nitrendipine-sensitive Ca2+ channels of intact cardiac myocytes in the presence of IGF1 by monitoring unidirectional Mn2+ influx measured as the quench of cytosolic fura-2 in electrically stimulated or K+-depolarized cells. Maximal channel activation was observed after 10 min of preincubation with IGF1, which gave an increase of 216 +/- 25%. Treatment with the protein kinase C inhibitors bisindolylmaleimide I and chelerythrine mimicked the augmentation effect of IGF1, whereas PMA blocked enhancement of Mn2+ influx by IGF1. These results demonstrate that acute IGF1 augments dihydropyridine-sensitive sarcolemmal Ca2+ channel activity and that protein kinase C may contribute to the regulation of cardiac Ca2+ channels by IGF1.
Assuntos
Canais de Cálcio/fisiologia , Coração/fisiologia , Fator de Crescimento Insulin-Like I/farmacologia , Sulfonamidas , Animais , Cálcio/metabolismo , Canais de Cálcio/efeitos dos fármacos , Carbazóis/farmacologia , Células Cultivadas , Cromonas/farmacologia , Citosol/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Indóis/farmacologia , Fator de Crescimento Insulin-Like I/fisiologia , Isoquinolinas/farmacologia , Cinética , Masculino , Manganês/metabolismo , Morfolinas/farmacologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Sarcolema/metabolismo , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Three new dihydroxyicosanoids, 12(R),13(R)-dihydroxyicosa-5(Z),8(Z),10(E),14(Z)-tetraenoic acid, 12(R),13(R)-dihydroxyicosa-5(Z),8(Z),10(E),14(Z),17(Z)-pentaeno ic acid and 10(R*),11(R*)-dihydroxyoctadeca-6(Z),8(E),12(Z)-trienoic acid, have been isolated from a previously unstudied temperate red marine alga, Farlowia mollis (Cryptonemiales, Rhodophyta). The structures of these new metabolites have been deduced from detailed nuclear magnetic resonance and mass spectrometry analyses on stabilized diacetate-methyl esters and stereochemistry deduced by 1H NMR couplings and CD analysis of a dibenzoate derivative. Collectively, these new natural products modulate fMLP-induced superoxide anion generation in human neutrophils, inhibit the conversion of arachidonic acid to lipoxygenase products by human neutrophils, and inhibit the functioning of the dog kidney Na+/K+ ATPase.
