Acute stimulation of glucose transport by histamine in cardiac microvascular endothelial cells.
The purpose of the present work was to study the acute regulation of glucose uptake in cultured cardiac endothelial cells (CEC). Two types of potential stimuli were considered: (1) agents that are known to acutely stimulate glucose transport (i.e., within minutes) in fat and muscle tissues and (2) agents that influence endothelial cell function. Among the former agents, neither insulin, nor catecholamines (adrenaline, dopamine, phenylephrine), nor serotonin affected the rate of glucose transport in CEC, while SH-group reagents (phenylarsine oxide, diamide or menadione) were inhibitory. Among the factors of the second group that were tested (heparin, ADP, histamine, bradykinin), histamine was found to stimulate glucose transport in CEC by 10-50%. This effect was concentration-dependent (with an EC50 value approximately equal to 12 microM) and reached a maximum within 5 min upon histamine addition. This stimulation of glucose transport was suppressed by pyrilamine (100 nM), a specific H1-receptor antagonist, but not by cimetidine (100 microM), a H2-selective antagonist. Northern blot and Western blot analysis of CEC extracts revealed the presence of the ubiquitous glucose transporter isoform GLUT1 mRNA and protein, but not of the 'insulin-regulatable' isoform GLUT4. In conclusion, this is the first report on an acute stimulation of glucose transport in cardiac endothelial cells, in particular, and in an insulin-unresponsive cell type, in general. The effect of histamine is most likely mediated by H1-receptors and cannot be accounted for by a recruitment of GLUT4.
Thomas
J
J
Institute of Physiology, Medical Faculty, RWTH Aachen, Germany.
Linssen
M
M
van der Vusse
G J
GJ
Hirsch
B
B
Rösen
P
P
Kammermeier
H
H
Fischer
Y
Y
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002927:Cimetidine / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology; D003847:Deoxyglucose / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006632:Histamine / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D009124:Muscle Proteins; D011738:Pyrilamine / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013438:Sulfhydryl Compounds
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D013438:Sulfhydryl Compounds; D000244:Adenosine Diphosphate; D002927:Cimetidine; D006632:Histamine; D003847:Deoxyglucose; D011738:Pyrilamine; D005947:Glucose