Hormonal regulation of Gi alpha level and adenylyl cyclase responsiveness.
Prolonged exposure of cells to adenylyl cyclase stimulatory hormonal factors can cause an increase in the level of membrane inhibitory G protein (Gi) alpha-subunits, while inhibitory receptor agonists have been reported to induce the opposite response. As studied in cultured rat cardiomyocytes, the beta-adrenoceptor-induced increase in the level of Gi alpha proteins is protein synthesis-dependent, is apparently not accompanied by an increase in G protein beta-subunits and results in a decreased adenylyl cyclase responsiveness. On the other hand, a decrease in Gi alpha level apparently results in sensitization of adenylyl cyclase stimulation. These data suggest that the up- or down-regulation of the level and activity of Gi protein alpha-subunits is a rather general cellular response, providing an intracellular negative feedback control against prolonged receptor activation.
Reithmann
C
C
Pharmakologisches Institut, Universität Heidelberg, Federal Republic of Germany.
Gierschik
P
P
Werdan
K
K
Jakobs
K H
KH
D036002:ADP Ribose Transferases; D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001427:Bacterial Toxins; D005098:Exotoxins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006728:Hormones / Q000502:physiology*; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000262:Adenylyl Cyclases; D001427:Bacterial Toxins; D005098:Exotoxins; D019204:GTP-Binding Proteins; D006728:Hormones; D009638:Norepinephrine; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A