Effect of Ca2(+)-channel agonists and antagonists on skeletal muscle sugar transport.
The purpose of this study was to determine whether changes in cellular Ca2+ caused by Ca2(+)-channel modifiers affect skeletal muscle sugar transport. Rat soleus muscles were isolated, and sugar transport was measured monitoring efflux of 3-O-methylglucose (3-MG). Muscles were "loaded" with 3-O-[methyl-14C]methyl-D-glucose in Krebs-Ringer-bicarbonate (KRB) media and then sequentially washed in radioisotope-free KRB. Cellular Ca2+ was modified by adding a Ca2+ agonist (BAY K 8644) and/or Ca2+ antagonists (nifedipine, nitrendipine, diltiazem) to the "load" and "wash" media. Alterations in cellular Ca2+ were determined from soleus muscle 45Ca2+ uptake measurements. Addition of 0.25 microM BAY K 8644 enhanced insulin-mediated 3-MG transport and 1 microM nifedipine prevented the agonist effect. A high concentration of BAY K 8644 (6 microM) led to increased basal but attenuated insulin-mediated 3-MG transport. Nifedipine (4 microM) and diltiazem (20 microM) blocked the BAY K 8644-induced changes in basal and insulin-mediated 3-MG transport. Nifedipine (4 microM) also attenuated the stimulation of cellular Ca2+ uptake by 6 microM BAY K 8644. Nitrendipine was unable to reverse the changes in basal or insulin-mediated 3-MG transport caused by BAY K 8644. These results indicate that a low concentration of BAY K 8644 enhanced insulin-stimulated skeletal muscle sugar transport, whereas a high concentration of the agonist led to a diminished ability of insulin to stimulate sugar transport. The effects of the Ca2+ agonist were presumably mediated through modulation of cellular Ca2+ as these effects were blunted by the Ca2+ antagonists.
Department of Physiology, Loyola University Stritch School of Medicine, Maywood, Illinois 60153.
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Sayeed
D019325:3-O-Methylglucose; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D050260:Carbohydrate Metabolism; D004110:Diltiazem / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D007328:Insulin; D008757:Methylglucosides; D019325:3-O-Methylglucose; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004110:Diltiazem; D009543:Nifedipine