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 mumol/l significantly inhibited glucagon secretion induced by 0.1 mumol/l clonidine (P less than 0.01, respectively), whereas 5 mumol/l mepacrine did not affect clonidine-induced glucagon secretion. Also, both 100 mumol/l acetylsalicylic acid (cyclooxygenase inhibitor) and 100 mumol/l caffeic acid (lipoxygenase inhibitor) significantly inhibited clonidine-induced glucagon secretion (P less than 0.01, respectively), whereas neither 10 mumol/l acetylsalicylic acid nor 10 mumol/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.
Koyama
K
K
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Hirose
H
H
Maruyama
H
H
Itoh
K
K
Kido
K
K
Saruta
T
T
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
D001095:Arachidonic Acids; D011942:Receptors, Adrenergic, alpha; D002110:Caffeine; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D005947:Glucose; D003000:Clonidine; D001241:Aspirin