Differential effects of proinsulin C-peptide fragments on Na+, K+-ATPase activity of renal tubule segments.
Proinsulin C-peptide has been shown to stimulate the activity of Na+ K+ ATPase of rat renal tubule segments. Thirty-six peptides and amino acids, corresponding to parts of the intact rat C-peptide and suitable controls were screened for capacity to stimulate Na+, K+-ATPase in an attempt to determine potential active sites in the C-peptide molecule. The carboxy-terminal tetra and penta peptides were found to elicit 92-103% of the intact molecule's activity, and the remaining segment, des-(27-31) C-peptide, did not possess stimulatory activity. Peptides from the middle C-peptide segment, however, centering around a GGPEAG sequence, stimulated Na+, K+-ATPase activity (36-80% of the intact molecule's effect) but this effect was not balanced by corresponding inactivity of other parts. Furthermore, it was paralleled by activity of a non-native dipeptide D-form. It is concluded that the latter effect and that of the middle segment may represent complex interactions other than the apparently specific effects of the C-terminal segment.
Ohtomo
Y
Y
Department of Woman and Child Health, Pediatric Unit, St. Göran's Children's Hospital, Stockholm, Sweden.
Bergman
T
T
Johansson
B L
BL
Jörnvall
H
H
Wahren
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002096:C-Peptide / Q000737:chemistry / Q000494:pharmacology; D005998:Glycine / Q000737:chemistry / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011384:Proinsulin / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism
D002096:C-Peptide; D009842:Oligopeptides; D010446:Peptide Fragments; D011384:Proinsulin; D000254:Sodium-Potassium-Exchanging ATPase; D005998:Glycine