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The action of blood serum from uremic rats and chronically hemodialyzed patients was investigated for effects on alpha 2-adrenoceptors labeled with 3H-clonidine. Compared to blood sera of rats and patients with normal kidney function, uremic serum significantly inhibited specific 3H-clonidine binding. In saturation experiments the density and affinity of alpha 2-adrenoceptors for 3H-clonidine was lowered by uremic serum. Heating, or trypsin or lipase treatment of the serum did not affect this phenomenon. The effect of the patient's serum could likewise be demonstrated after hemodialysis treatment. The presence of an allosteric regulating substance for clonidine binding to adrenoceptors could at least partially explain the altered and attenuated action of this drug in renal insufficiency.

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The interactions of the anticoagulant Heparin with the alpha-2-adrenoceptor in rat brain cortex membranes were investigated. Binding experiments with 3H-Clonidine were performed in both the absence and presence of Heparin. 1 uM Na-Heparin caused a significant decrease in the maximal number of binding sites (Bmax) from 129.4 fmol/mg protein to 93.7 fmol/mg protein with an associated decrease in affinity (KD = 0.79 pM vs. KD = 1.53 pM) of these binding sites. Addition of Na+-Heparin to 3H-Clonidine (3.1 nM) labelled membranes inhibited 50% of specific 3H-Clonidine binding (IC50) at a concentration of 0.95 uM. Based on our findings we conclude that the simultaneous long term administration of Na-Heparin and the antihypertensive agonist Clonidine should be regarded under consideration of the inhibitory effect of Na-Heparin to the alpha-2-adrenoceptors.

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