Influence of catecholaminergic and serotonergic receptor antagonists on the hyperglycaemic response to the neuroglucopaenic agent, 2-deoxy-D-glucose.
The intravenous administration of 2-deoxy-D-glucose (2-DG) to conscious catheterised rats dose-dependently increased the levels of glucose in plasma throughout the analysis (60 min); the levels of insulin in plasma remained unchanged, except for an early significant decrease in rats treated with the largest dose (1 g/kg). Pretreatment (10 min beforehand) with the beta 2-adrenoceptor antagonist, ICI 118,551 (3 mg/kg) or the alpha 2-adrenoceptor antagonist, idazoxan (1 mg/kg) decreased the rise in levels of glucose in plasma elicited by 2-DG (250 mg/kg). Conversely, the alpha 1-adrenoceptor antagonist, prazosin (1 mg/kg) or the dopaminergic receptor blocker, haloperidol (0.5 mg/kg) amplified the hyperglycaemic response to 2-DG. Previous administration of either the 5-HT1A/5-HT2 receptor antagonist, spiperone (3 mg/kg), the 5-HT1/5-HT2 receptor antagonist, methysergide (1 mg/kg), the 5-HT1C/5-HT2 receptor antagonist, ritanserin (1 mg/kg) or the 5-HT3 receptor antagonist, ICS 205.930 (0.1 mg/kg) did not affect 2-DG-induced hyperglycaemia. On the other hand, the mixed 5-HT1A/5-HT1B/beta-adrenoceptor antagonist, (-)-propranolol (5 mg/kg) and the 5-HT1/5-HT2 receptor antagonist, methiotepin (1 mg/kg), respectively, diminished and amplified the hyperglycaemia elicited by 2-DG. Lastly, in rats pretreated with prazosin (1 mg/kg, 30 min beforehand), an additional pretreatment (10 min beforehand) with prazosin or methiotepin (both at 1 mg/kg) did not further amplify the hyperglycaemic response to 2-DG. These results indicate that 2-DG-induced hyperglycaemia is mediated by alpha 2- and beta 2-adrenoceptors and amplified by alpha 1-adrenoceptor blockade. Conversely, neither 5-HT1, 5-HT2 nor 5-HT3 receptors played a role in the hyperglycaemic response to 2-DG.
Baudrie
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V
Laboratoire de Pharmacologie, Groupe de Neuropharmacologie, CNRS, CHU Necker, Paris, France.
Chaouloff
F
F
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D018680:Cholinergic Antagonists; D003847:Deoxyglucose / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012702:Serotonin Antagonists
D001786:Blood Glucose; D002395:Catecholamines; D018680:Cholinergic Antagonists; D007328:Insulin; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D012702:Serotonin Antagonists; D003847:Deoxyglucose