ARACHIDONIC-ACID METABOLITES AND ALPHA-2-ADRENOCEPTOR-MEDIATED GLUCAGON-SECRETION IN RATS

Effects of phospholipase A2 inhibitor, cyclooxygenase inhibitor and lipoxygenase inhibitor on glucagon secretion induced by the alpha-2-adrenergic agonist clonidine were studied in the isolated perfused rat pancreas. The phospholipase A2 inhibitor mepacrine at 25 and 50-mu-mol/l significantly inhibited glucagon secretion induced by 0.1-mu-mol/l clonidine (P < 0.01, respectively), whereas 5-mu-mol/l mepacrine did not affect clonidine-induced glucagon secretion. Also, both 100-mu-mol/l acetylsalicylic acid (cyclooxygenase inhibitor) and 100-mu-mol/l caffeic acid (lipoxygenase inhibitor) significantly inhibited clonidine-induced glucagon secretion (P < 0.01, respectively), whereas neither 10-mu-mol/l acetylsalicylic acid nor 10-mu-mol/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 alpha-2-adrenergic receptors in perfused rat pancreas.