Mammalian urinary bladder permeability is altered by cationic proteins: modulation by divalent cations.
It was previously demonstrated that protamine sulfate (PS, a cationic polypeptide) as well as synthetic cationic polypeptides (CpP, e.g., polylysine and polyarginine) caused an increase in the apical membrane conductance of the mammalian urinary bladder epithelium that was voltage dependent. The membrane conductance induced by these CpP was mediated by a saturable binding site and was partially blocked by CpP (self-inhibition). The PS-induced membrane conductance can be modified by polyvalent cations at three sites. The first site was to competitively inhibit the interaction of PS with an apical membrane binding site. The second site was to reversibly block the conductance induced by PS. The relative binding affinity (block of PS-induced conductance) sequence was as follows: UO2(2+) > La3+ > Mn2+ > Ba2+ > or = Ca2+ > Sr2+. Although La3+, Mn2+, Ba2+, Ca2+, and Sr2+ inhibited > or = 81% of the PS-induced conductance, UO2(2+) inhibited only 51% and Mg2+ was without effect. The third site was to increase the rate of loss of the PS-induced conductance from the apical membrane. Although neither carbodiimides (carboxyl group reactive reagents) nor neuraminidase (cleaves sialic acid residues) altered the effect of PS on the urinary bladder conductance, PS increased the conductance of lipid bilayers composed of negatively charged phospholipids. A candidate for the binding site might be the negatively charged phosphate groups of membrane lipids.
Tzan
C J
CJ
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555.
Berg
J R
JR
Lewis
S A
SA
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004553:Electric Conductivity; D004848:Epithelium / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D011479:Protamines / Q000494:pharmacology*; D011817:Rabbits; D001743:Urinary Bladder / Q000378:metabolism*
D002413:Cations, Divalent; D011479:Protamines; D008274:Magnesium; D002118:Calcium