Role of alpha1A-adrenoceptor in the regulation of glucose uptake into white adipocyte of rats in vitro.
In an attempt to know the functional role of alpha1A-adrenoceptors in adipose tissue, white adipocytes (WAT) of Wistar rats were used to investigate the change of glucose uptake after pharmacological activation of alpha1-adrenoceptors. Methoxamine enhanced the uptake of radioactive glucose into isolated WAT in a concentration-dependent manner. Translocation of glucose transporter (GLUT4) from cytosol to membrane was also stimulated with methoxamine. Action of methoxamine to raise glucose uptake was abolished in WAT pre-incubated with the antagonists, both tamsulosin and WB 4101, at concentrations sufficient to block alpha1A-adrenoceptors. However, chlorethylclonidine (CEC). the antagonist of alpha1B-adrenoceptors, showed the inhibition of methoxamine-induced action only at a higher concentration. Even under the treatment with maximal concentration of CEC, methoxamine can produce action about 80% of the vehicle-treated control. The major role of alpha1A-adrenoceptors in the stimulation of glucose uptake by methoxamine can thus be considered. In the presence of specific inhibitor of phospholipase C (PLC), U73312, methoxamine-stimulated glucose uptake into WAT was reduced in a concentration-dependent manner and U73343, the negative control of U73312, did not affect the action of methoxamine. Moreover, chelerythrine and GF 109203X diminished the methoxamine-stimulated glucose uptake at a concentration sufficient to inhibit protein kinase C (PKC). Inhibition of phosphoinositide-3 kinase (PI-3 kinase) by LY294002 also abolished methoxamine-stimulated glucose uptake. Therefore. the obtained data suggest that an activation of alpha1A-adrenoceptors, presence in WAT, by agonist and/or neurotransmitter may increase the glucose uptake via PLC-PKC pathway and the activation of PI-3 kinase.
Cheng
J T
JT
Department of Pharmacology, College of Medicine, National Cheng Kung, University, Tainan City, Taiwan, ROC. jtcheng@mail.ncku.edu.tw
Liu
I M
IM
Yen
S T
ST
Chen
P C
PC
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001693:Biological Transport, Active / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008729:Methoxamine / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009124:Muscle Proteins; D010617:Phenanthridines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011224:Prazosin / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D000077409:Tamsulosin; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
C547715:Adra1a protein, rat; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000470:Alkaloids; D053119:Benzophenanthridines; D002867:Chromones; D004146:Dioxanes; D004791:Enzyme Inhibitors; D004963:Estrenes; D051275:Glucose Transporter Type 4; D007211:Indoles; D008301:Maleimides; D009004:Monosaccharide Transport Proteins; D009025:Morpholines; D009124:Muscle Proteins; D010617:Phenanthridines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011760:Pyrrolidinones; D018340:Receptors, Adrenergic, alpha-1; C495694:Slc2a4 protein, rat; D013449:Sulfonamides; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C074854:U 73343; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C051731:chlorethylclonidine; D003847:Deoxyglucose; C016299:chelerythrine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D011493:Protein Kinase C; D010738:Type C Phospholipases; D000077409:Tamsulosin; D008729:Methoxamine; D005947:Glucose; C070515:bisindolylmaleimide I; D003000:Clonidine; D011224:Prazosin