Involvement of alpha-2 adrenergic receptor subtypes in hyperglycemia.
Alpha-2 adrenoceptor stimulation induces in the mouse a hyperglycemic response which is accompanied by a concomitant inhibition of insulin secretion. To test the possibility that one of the postulated subtypes of alpha-2 adrenoceptors is preferentially implicated in this response, we compared the interaction of several drugs with known selectivity toward alpha-2A or alpha-2B adrenoceptor subtypes in our model. The alpha-2A preferential agonist oxymetazoline induced in the mouse a hyperglycemic response similar to that of the nonselective alpha-2 adrenoceptor agonist UK 14.304. This hyperglycemic response to oxymetazoline was accompanied by a concomitant inhibition of insulin release. Both the effect on glycemic level and the inhibition of insulin release by oxymetazoline were antagonized by the alpha-2 adrenoceptor antagonist idazoxan. The alpha-2B preferential antagonists ARC-239, prazosin or chlorpromazine failed to block the modifications in both glycemic and insulin levels induced by alpha-2 adrenoceptor stimulation. The nonselective antagonists rauwolscine, yohimbine, WY 26703, phentolamine and corynanthine, as well as the receptor antagonists with alpha-2A selectivity like WB 4101, idazoxan and tolazoline, dose-dependently antagonized both the glycemic and the insulin responses to UK 14.304. A positive correlation was obtained between the potencies of these drugs in antagonizing the hyperglycemic response to UK 14.304 and their affinities for alpha-2A adrenergic receptors (r = 0.918, P less than .001) but no correlation was obtained with their affinities for alpha-2B adrenergic receptors (r = 0.048, P = N.S.)(ABSTRACT TRUNCATED AT 250 WORDS)
Angel
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Department of Biology, Synthélabo Recherche (Laboratoires d'Etudes et de Recherches Synthélabo, Paris, France.
Niddam
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Langer
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D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D000068438:Brimonidine Tartrate; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D004347:Drug Interactions; D006943:Hyperglycemia / Q000139:chemically induced* / Q000517:prevention & control; D019329:Idazoxan; D007093:Imidazoles / Q000037:antagonists & inhibitors*; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D010109:Oxymetazoline / Q000037:antagonists & inhibitors*; D011810:Quinoxalines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D004146:Dioxanes; D004147:Dioxins; D007093:Imidazoles; D007328:Insulin; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D010109:Oxymetazoline; D019329:Idazoxan