Insulin and IGF I receptor-mediated Na+ transport in toad urinary bladders.
We compared the concentration dependence of insulin- and insulin-like growth factor I (IGF I)-stimulated Na+ transport with ligand-receptor affinities in the urinary bladder of the toad Bufo marinus. Threshold, half-maximal, and maximal natriferic concentrations of both peptides were approximately 0.1, 1, and 10 nM, respectively. Amiloride, but not ethyl isopropyl amiloride, (10(-5) M), abolished Na+ transport. Maximal responses to either peptide rendered the tissue insensitive to challenge with the other. Separate insulin and IGF I receptors were identified by equilibrium binding and polyacrylamide gel electrophoresis of cross-linked ligand-receptor complexes. For both peptides, half-maximal binding occurred at 3-10 nM; crossover binding to the other receptor occurred with 10- and 100-fold lower affinity. Thus, in this model "high-resistance" renal epithelium, 1) ligand binding to specific insulin and IGF I receptors stimulates transcellular Na+ flux, 2) the natriferic effects of insulin and IGF I apparently depend on activation of apical Na+ channels rather than Na+-H+ antiporters, and 3) the natriferic pathways activated by insulin and IGF I appear to converge subsequent to ligand-receptor binding but before the final transport ("effector") step(s).
Blazer-Yost
B L
BL
Department of Medicine, Veterans Administration Medical Center, Philadelphia, Pennsylvania.
Cox
M
M
Furlanetto
R
R
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002024:Bufo marinus; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011972:Receptor, Insulin / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D013002:Somatomedins / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D000584:Amiloride; D012964:Sodium; D011972:Receptor, Insulin; C039614:ethylisopropylamiloride