Liebl, B. and Anhäupl, T. and Haen, Ekkehard and Remien, J.
Effect of thiols on beta 2-adrenoceptors in human mononuclear leucocytes.
Naunyn-Schmiedeberg's archives of pharmacology 338 (5), pp. 523-528.
The effect of the disulfide reducing agent dithiothreitol (DTT) and other thiols on binding of the beta-adrenoceptor antagonist (-)-125iodocyanopindolol (125ICYP) to human mononuclear leucocytes (MNL) was investigated. Saturation experiments and dissociation kinetics revealed two classes of specific 125ICYP binding sites, one of high and the other of low affinity, respectively. In intact MNL DTT caused a decrease in specific binding. This was due almost selectively to a decrease in the affinity of high affinity binding sites, which decreased gradually in a concentration-dependent manner to the affinity of low affinity binding sites. In MNL membranes DTT decreased not only the affinity but also the number of high affinity binding sites. The DTT effect was completely reversible by simple reoxidation on air. The structural isomers (+/-)-DTT. (-)-DTT and dithioerythritol revealed identical effects on specific binding, whereas the monothiols mercaptoethanol and alpha-monothioglycerol, having a lower redox potential, were considerably less effective. In the same concentration range that influenced specific binding. DTT stimulated intracellular cAMP production. These results suggest functionally important disulfide bridges which regulate the affinity of beta-adrenoceptor binding sites in human MNL. They stabilize the receptor in a high affinity state; their reduction causes the conversion of the high affinity state into a low affinity state in a process associated with stimulation of adenylate cyclase. Available evidence indicates that a similar transformation is made by beta-adrenoceptor agonists. Consequently low affinity 125ICYP binding sites preexistent in untreated cells could represent a reduced receptor state resulting from agonist-receptor interaction in vivo.
|Institutions:|| Medicine > Lehrstuhl für Psychiatrie und Psychotherapie|
|Dose-Response Relationship, Drug||MESH|
|Receptors, Adrenergic, beta/drug effects||MESH|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||18 Feb 2011 10:27|
|Last Modified:||21 Jul 2011 02:07|