Growth hormones reverse desensitization of P2Y(2) receptors in rat mesangial cells.
Rat glomerular mesangial cells (GMC) express P2Y(2) purinoceptors and respond to nucleotide stimuli with a transient increase in the cytosolic Ca(2+) concentration and the receptors desensitize upon repeated stimulation with nucleotide. We demonstrate that there is a cross-talk from the signaling of tyrosine kinase to P2Y(2) receptors. For most cells repeated applications of ATP completely abolished the response, as did activation of PKC with 500 nM PMA. In contrast, preincubation with the PKC inhibitor chelerythrine (100 nM) prevented desensitization. Desensitization after application of ATP was reversed by subsequent incubation with PDGF-BB (50 ng/ml) or insulin (660 mU/ml). We conclude that the desensitization is caused by phosphorylation due to PKC and is under the control of growth factors. The findings support the hypothesis that growth hormones potentiate nucleotides as proinflammatory mediators and we hypothesize that they have bearing on the hyperfiltration seen in diabetes.
Gutierrez
A M
AM
Department of Physiology and Medical Biophysics, Biomedical Center, Uppsala, S-751 23, Sweden.
Lou
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X
Erik
A
A
Persson
G
G
Ring
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000470:Alkaloids; D000818:Animals; D000077214:Becaplermin; D053119:Benzophenanthridines; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D058473:Receptors, Purinergic P2Y2; D014544:Uridine Triphosphate / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007328:Insulin; C546387:P2ry2 protein, rat; D010617:Phenanthridines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D000077214:Becaplermin; D000255:Adenosine Triphosphate; C016299:chelerythrine; D011493:Protein Kinase C; D002118:Calcium; D014544:Uridine Triphosphate