Dopamine analog-induced hyperglycemia in rats: involvement of the adrenal medulla and the endocrine pancreas.
The following synthetic, structural analogs of dopamine (DA) were examined for their ability to produce hyperglycemia in conscious unrestrained rats: APO (apomorphine), RDS-127 (2-di-n-propylamino-4,7-dimethoxyindane), di-n-propyldopamine, 2-di-n-propylamino-5,6-dihydroxytetralin, 2-dimethylamino-6,7-dihydroxytetralin, lergotrile, pergolide, bromocriptine and d-amphetamine. All the compounds demonstrated dose- and time-dependent hyperglycemic actions. The most potent DA analog to induce hyperglycemia was 2-di-n-propylamino-5,6-dihydroxytetralin (0.18 mumol/kg) and, at the doses used, 2-dimethylamino-6,7-dihydroxytetralin produced the greatest elevation in blood glucose (227% control). APO and RDS-127 were used in experiments designed to provide additional mechanistic information concerning their hyperglycemic action. The hyperglycemia produced by APO or RDS-127 was blocked by adrenalectomy, adrenodemedullation or prior administration of pimozide, a DA receptor antagonist. Phentolamine, an alpha adrenergic receptor antagonist had no effect on the hyperglycemia induced by APO or RDS-127. Oral glucose tolerance tests indicated that APO and RDS-127 caused abnormal glucose tolerance and inhibited the compensatory increase in serum immunoreactive insulin. These effects were prevented by pimozide or phentolamine pretreatment. The potencies of the compounds to produce increases in serum glucose concentrations (SG), inhibit the accumulation of DOPA using the in vivo gamma-butyrolactone procedure (DOPA) and inhibit food intake (FI) were subjected to correlation analysis. Positive correlations were found for FI vs. DOPA, r = 0.96; SG vs. decreases DOPA, r = 0.98 and SG vs. FI, r = 0.98.(ABSTRACT TRUNCATED AT 250 WORDS)
D000313:Adrenal Medulla / Q000187:drug effects*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis*; D001971:Bromocriptine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004873:Ergolines / Q000031:analogs & derivatives / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D010479:Pergolide; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D001786:Blood Glucose; D004873:Ergolines; D007189:Indans; D007328:Insulin; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D010479:Pergolide; D001971:Bromocriptine; D004295:Dihydroxyphenylalanine; C015842:2-(N,N-dipropyl)amino-5,6-dihydroxytetralin; C020895:N,N-di-n-propyldopamine; C016893:2-(N,N-dimethylamino)-6,7-dihydroxytetralin; C035604:2-N,N-di-n-propylamino-4,7-dimethoxyindan; D001058:Apomorphine; C031875:lergotrile; D003913:Dextroamphetamine; D004298:Dopamine