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• W2075209490 abstract "We studied the effects of various (β-adrenoceptor βAR) antagonists and local anesthetics (LAs), i.e. substances possessing one basic and one lipophilic domain each, on activation of regulatory heterotrimeric guanine nucleotide-binding proteins (G-proteins). In membranes of differentiated HL-60 cells, propranolol activated high-affinity GTP hydrolysis with a half-maximal effect at 0.19 mM and a maximum at 1 mM. There was a close correlation between the log Q values (logarithm of the octanol: water partition coefficient) of βAR antagonists and the logarithm of their effectiveness at activating GTPase (EC 3.6.1.-) in HL-60 membranes. The lipophilic LA, tetracaine, was also an effective activator of GTPase in HL-60 membranes, whereas more hydrophilic LAs were less stimulatory (bupivacaine and lidocaine) or even inhibitory (procaine). Propranolol and tetracaine also stimulated binding of guanosine 5'-O-[3-thio]triphosphate (GTP[γS]) to HL-60 membranes, but their stimulatory effects on GTP[γS] binding were smaller than on GTP hydrolysis. The stimulatory effects of propranolol and tetracaine on GTPase and GTP[γS] binding were inhibited by pertussis toxin. Propranolol and tetracaine effectively activated GTP hydrolysis of a reconstituted mixture of bovine brain Gi/Go-proteins, but the concentrations of substances needed for GTPase activation were higher than in HL-60 membranes. Procaine showed stimulatory effects on the GTPase of Gi/Go-proteins. Our data show that βAR antagonists and LAs activate pertussis toxin-sensitive G-proteins, presumably through interaction with the C-terminus of their α-subunits. Apparently, the lipophilic domain of βAR antagonists and LAs is more important for G-protein activation than the basic domain. We discuss the possibility that activation of nucleoside diphosphate kinase by βAR antagonists and LAs contributes to their stimulatory effects on GTP hydrolysis in HL-60 membranes." @default.
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• W2075209490 date "1994-05-01" @default.
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• W2075209490 title "Lipophilic β-adrenoceptor antagonists and local anesthetics are effective direct activators of g-proteins" @default.
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• W2075209490 doi "https://doi.org/10.1016/0006-2952(94)90307-7" @default.
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