Mapping of the beta 2-adrenoceptor on Chang liver cells. Differences between high- and low-affinity receptor states.
Receptor mapping procedures based on the methodology of Crippen are used to study the beta 2-adrenergic receptor system in intact Chang liver cells. In cases of agonists, the presence of both a low- and high-affinity receptor state is assumed, whereas antagonists bind to the low-affinity state only. The high-affinity state is considered to contain the "functional" binding site responsible for formation of the second messenger (cAMP), whereas the low-affinity state is assumed to be the "true" (physiological) low-affinity state. Both receptor states are taken into account in the receptor mapping process. Characterization of the high- and low-affinity states made it possible to identify features that make a state an antagonist or agonist. The receptor model found for the low-affinity state of the beta-adrenergic receptor present in an intact cell system is compared to the low-affinity state previously obtained for this receptor present on a membrane preparation of the bovine skeletal muscle in the presence of high amounts of Gpp(NH)p guanosine 5'-(beta, gamma-imidotriphosphate). Remarkable differences are found between the two receptor models. The tentative conclusion is drawn that these differences in low-affinity states most probably are artificial and are caused by the different pharmacological properties (e.g., intrinsic activity) of the labeled ligands used in displacement experiments for determining the affinities of the drugs.
Donné-Op den Kelder
G M
GM
Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Bultsma
T
T
Timmerman
H
H
Rademaker
B
B
D002462:Cell Membrane / Q000032:analysis; D002478:Cells, Cultured; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006860:Hydrogen Bonding; D020120:Iodocyanopindolol; D008099:Liver / Q000032:analysis*; D008958:Models, Molecular; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011487:Protein Conformation; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000378:metabolism; D011954:Receptors, Dopamine / Q000032:analysis; D017448:Receptors, Dopamine D2; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D006165:Guanylyl Imidodiphosphate; D020120:Iodocyanopindolol; D010869:Pindolol