title: Alpha 2-adrenergic blockade prevents hyperglycemia and hepatic glutathione depletion in nickel-injected rats.
abstract: To study the involvement of the adrenergic system in nickel-induced hyperglycemia and hepatic glutathione depletion in rats, several adrenergic antagonists (phentolamine, prazosin, yohimbine, and propranolol) were administered in a single ip injection before acute nickel treatment (ip injection). Moreover, the effects of nickel on adrenalectomized rats were investigated. Hyperglycemia was suppressed by either alpha-antagonist phentolamine or alpha 2-antagonist yohimbine. Such blockade coincided with the prevention of the hypoinsulinemic response to nickel, which occurred simultaneously to hyperglycemia. Nickel-induced hyperglucagonemia remained almost unaltered by pretreatment with adrenergic antagonists. In adrenalectomized animals treated with nickel, hyperglycemia was attenuated, whereas hypoinsulinemia still persisted. Therefore, catecholamines seemed to participate in nickel-induced hyperglycemia, directly, i.e., stimulating glucose output from liver, or by modulating insulin secretion throughout alpha 2-adrenoreceptor stimulation in pancreatic islets. Hepatic glutathione depletion caused by nickel was prevented by either alpha 1-antagonist prazosin or alpha 2-antagonist yohimbine. Interestingly, adrenalectomy did not alter the drop in hepatic GSH induced by nickel treatment. Overall results suggest that the effects observed after acute nickel exposure were caused by a combined action of catecholamines released from the adrenal glands and those released at the efferent nerves. Such events have been found to be mediated by alpha 2-adrenergic receptors.
authors.affiliation: Unitat de Bioquímica, Facultat de Ciències Químiques, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Alvarez
authors.forename: C
authors.initials: C
authors.lastname: Bladé
authors.forename: J
authors.initials: J
authors.lastname: Cartañà
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D005260:Female; D005934:Glucagon / Q000097:blood; D005978:Glutathione / Q000378:metabolism*; D006943:Hyperglycemia / Q000139:chemically induced* / Q000517:prevention & control; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009532:Nickel / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D007328:Insulin; D015016:Yohimbine; D009532:Nickel; D005934:Glucagon; D011433:Propranolol; D005978:Glutathione; D011224:Prazosin; D010646:Phentolamine