Effects of phospholipase A2 inhibitor, cyclooxygenase inhibitor and lipoxygenase inhibitor on glucagon secretion induced by the α2-adrenergic agonist clonidine were studied in the isolated perfused rat pancreas. The phospholipase A2 inhibitor mepacrine at 25 and 50 μmol/l significantly inhibited glucagon secretion induced by 0.1 μmol/l clonidine (P < 0.01, respectively), whereas 5 μmol/l mepacrine did not affect clonidine-induced glucagon secretion. Also, both 100 μmol/l acetylsalicilic acid (cyclooxygenase inhibitor) and 100 μmol/l caffeic acid (lipoxygenase inhibitor) significantly inhibited clonidine-induced glucagon secretion (P < 0.01, respectively), whereas neither 10 μmol/l acetylsalicylic acid nor 10 μmol/l caffeic acid affected clonidine-induced glucagon secretion. None of the drugs at the tested concentrations affected insulin secretion at a glucose concentration of 5.5 mmol/l. These results suggest that not only cyclooxygenase metabolites but also lipoxygenase metabolites are involved in the stimulation of glucagon secretion mediated through the α2-adrenergic receptors in perfused rat pancreas.
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