Structural basis of the function of endothelin receptor.
Endothelin receptor is a good model for analysis of the function of heptahelical G-protein coupled receptor. In ligand binding to the heptahelical receptor, the receptor has two functions, i.e. 'message' and 'address' functions. Each function has been assigned to different domain of the receptor. A different part of the ligand structure also corresponds to each domain of the receptor. Classically, classification of receptor has been done according to the difference of address domain, i.e. affinity difference of the receptor. However, present results predict that the classification of receptor is also possible according to the message domain. After stimulation of ET receptor by a ligand, the receptor transmits a signal to G-protein. Several kinds of G-proteins can possibly be activated. Different structural domains of the receptor are assigned to the coupling of the different Galpha-protein. Activated G-protein transmits the message to effector. Each Galpha-protein acts on different target molecules, resulting in different responses. However, the activation of each Galpha-protein presumably depends on its intracellular level. Even if the same receptor is activated with the same ligand, resulting final response is different from cell to cell. Therefore, classification of receptor according to the function of the receptor is difficult.
Masaki
T
T
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Ninomiya
H
H
Sakamoto
A
A
Okamoto
Y
Y
D000818:Animals; D019332:Endothelin-1 / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D017466:Receptors, Endothelin / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000502:physiology
D019332:Endothelin-1; D017466:Receptors, Endothelin; D019204:GTP-Binding Proteins