Modification of ligand binding to membranes by a soluble acceptor. Alpha-1-acid glycoprotein attenuates 3H-imipramine binding to cerebral membranes.
The effect of individual plasma proteins on the binding of 3H-imipramine (3H-IMI) was investigated, using rat cerebral membranes as the binding site source. Addition of alpha-1-acid glycoprotein (aAGLP) to an incubation medium containing 4 nm 3H-IMI resulted in a concentration-dependent inhibition of 3H-IMI binding, with an IC50 value of 0.53 microM. Albumin (0.7 mM) and gamma globulin (3 microM) had no apparent effect. Scatchard analyses of 3H-IMI binding in the presence and absence of 0.5 microM aAGLP revealed that the inhibition of 3H-IMI binding was associated with an increased Kd, with no appreciable change in Bmax. The inhibitory action of platelet-free plasma (PFP) on 3H-IMI binding to cerebral membranes was eliminated after treatment of PFP with specific antibodies to aAGLP. It is suggested that the inhibition of 3H-IMI binding to cerebral membranes by PFP is due, at least partially, to the presence of aAGLP in the plasma. The observed inhibitory effect is consistent with a competition for the ligand between the membrane binding site and the soluble protein acceptor. These findings may explain the serum effect confounding radioreceptor assays of various drugs.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins; D007099:Imipramine / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009961:Orosomucoid / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013570:Synaptic Membranes / Q000187:drug effects* / Q000378:metabolism; D005719:gamma-Globulins / Q000494:pharmacology
D002352:Carrier Proteins; D009961:Orosomucoid; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; D005719:gamma-Globulins; C027775:imipramine receptor; D012710:Serum Albumin, Bovine; D007099:Imipramine