C-peptide stimulates rat renal tubular Na+, K(+)-ATPase activity in synergism with neuropeptide Y.
This study was performed in order to test the hypothesis that the connecting peptide of proinsulin, C-peptide, might in itself possess biological activity. Renal tubular Na+, K(+)-ATPase, which is a well-established target for many peptide hormones, was chosen as a model. Rat C-peptide (I) was found to stimulate Na+, K(+)-ATPase activity in single, proximal convoluted tubules dissected from rat kidneys. C-peptide increased the Na+ affinity of the enzyme and all subsequent studies were performed at non-saturating Na+ concentrations. C-peptide stimulation of Na+, K(+)-ATPase activity occurred in a concentration-dependent manner in the dose range 10(-8)-10(-6) mol/l. The presence of neuropeptide Y, 5 x 10(-9) mol/l, enhanced this effect and stimulation of Na+, K(+)-ATPase activity then occurred in the C-peptide dose range 10(-11)-10(-8) mol/l. C-peptide stimulation of Na+, K(+)-ATPase activity was abolished in tubules pretreated with pertussis toxin. It was also abolished in the presence of FK 506, a specific inhibitor of the Ca2(+)-calmodulin-dependent protein phosphatase 2B. These results indicate that C-peptide stimulates Na+, K(+)-ATPase activity, probably by activating a receptor coupled to a pertussis toxin-sensitive G-protein with subsequent activation of Ca2(+)-dependent intracellular signalling pathways.
Ohtomo
Y
Y
Department of Woman and Child Health, St. Göran's Children's Hospital, Karolinska Institute, Stockholm, Sweden.
Aperia
A
A
Sahlgren
B
B
Johansson
B L
BL
Wahren
J
J
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004357:Drug Synergism; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D009478:Neuropeptide Y; D010566:Virulence Factors, Bordetella; D012964:Sodium; D037342:Pertussis Toxin; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D016559:Tacrolimus