TY - JOUR
T1 - Interaction of clonidine with human placental Na+-H+ exchanger
AU - Ganapathy, Malliga E.
AU - Leibach, Frederick H.
AU - Mahesh, Virendra B.
AU - Devoe, Lawrence D.
AU - Ganapathy, Vadivel
N1 - Funding Information:
Acknowledgements-Thisw ork was, in part, supportedb y NIH Grant AM 28389to F. H. L. and a Medical College of GeorgiaR esearchI nstituteg rantt o V. G. The authors wisht o thankM rs. Ida 0. Thomasf or her experts ecretarial assistanceT. his is ContributionN o. 0960f rom the Department of Cell and Molecular Biology.
PY - 1986/11/15
Y1 - 1986/11/15
N2 - The effect of clonidine, an α2-adrenergic receptor agonist, on the Na+-H+ exchanger in human placental brush-border membrane vesicles was examined. The exchanger was inhibited by clonidine. The inhibition was freely reversible, and the apparent inhibition constant for the process was 250 μM. The nature of inhibition was found to be competitive with respect to Na+. The Dixon plot ( solI v versus clonidine concentration) was linear (r2 = 0.998), indicating the interaction of the drug with a single site on the exchanger protein. Similar kinetic analyses with amiloride, a potassium-sparing diuretic, and cimetidine, a histamine type II receptor antagonist, revealed that these drugs also inhibited the Na+-H+ exchanger by interacting with a single site on the protein. The presence of clonidine increased the intercepts without affecting the slopes of the l v versus amiloride concentration and the l v versus cimetidine concentration plots. These results demonstrate that all three drugs, amiloride, cimetidine and clonidine, interact with the human placental Na+-H+ exchanger at a single site in a mutually exclusive manner, and the site of interaction is identical with the Na+-binding site on the external surface of the exchanger protein.
AB - The effect of clonidine, an α2-adrenergic receptor agonist, on the Na+-H+ exchanger in human placental brush-border membrane vesicles was examined. The exchanger was inhibited by clonidine. The inhibition was freely reversible, and the apparent inhibition constant for the process was 250 μM. The nature of inhibition was found to be competitive with respect to Na+. The Dixon plot ( solI v versus clonidine concentration) was linear (r2 = 0.998), indicating the interaction of the drug with a single site on the exchanger protein. Similar kinetic analyses with amiloride, a potassium-sparing diuretic, and cimetidine, a histamine type II receptor antagonist, revealed that these drugs also inhibited the Na+-H+ exchanger by interacting with a single site on the protein. The presence of clonidine increased the intercepts without affecting the slopes of the l v versus amiloride concentration and the l v versus cimetidine concentration plots. These results demonstrate that all three drugs, amiloride, cimetidine and clonidine, interact with the human placental Na+-H+ exchanger at a single site in a mutually exclusive manner, and the site of interaction is identical with the Na+-binding site on the external surface of the exchanger protein.
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U2 - 10.1016/0006-2952(86)90016-X
DO - 10.1016/0006-2952(86)90016-X
M3 - Article
C2 - 3022744
AN - SCOPUS:0023035749
SN - 0006-2952
VL - 35
SP - 3989
EP - 3994
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 22
ER -