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• W2008955080 endingPage "2028" @default.
• W2008955080 startingPage "2021" @default.
• W2008955080 abstract "The alpha 2-adrenergic receptor-mediated stimulation of GTPase activity was investigated in human platelet membranes. The stimulatory effect of (-)-epinephrine was strictly dependent on Mg2+ and derived from a high-affinity GTPase activation. (-)-Epinephrine and (-)-norepinephrine stimulated GTPase activity in a concentration-dependent manner with EC50 values of 200 and 600 nM, respectively. These effects were stereospecific, since (+/-)-epinephrine, (+/-)-norepinephrine, and (+)-epinephrine were less potent in stimulating the enzyme activity with EC50 values of 4, 1 and 3 microM, respectively. Thrombin also stimulated GTPase activity concentration dependently with an EC50 value of 0.02 U/mL. The maximal effects of (-)-epinephrine, (-)-norepinephrine, and thrombin were not additive in any combination. Clonidine did not stimulate GTPase activity, whereas another synthetic alpha 2-adrenergic agonist, p-aminoclonidine, had the characteristics of a partial agonist. The rank order of potency for antagonists to inhibit the activation of GTPase by 1 microM (-)-epinephrine was yohimbine = rauwolscine > idazoxan = oxymetazoline = phentolamine = WB4101 = (+)-mianserin > (-)-mianserin > prazosin > (-)-propranolol. Negative logarithms of the IC50 values of these antagonists corresponded well with the negative logarithmic values of Ki(pKi) for the alpha 2A-adrenergic receptors determined by a receptor-binding technique in human platelets. These results indicate that epinephrine stimulates high-affinity GTPase activity of G proteins (putatively Gi2), which are also coupled with thrombin receptors, in a Mg(2+)-dependent and stereospecific manner, via alpha 2A-adrenergic receptor activation in human platelet membrane preparations." @default.
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• W2008955080 date "1993-12-01" @default.
• W2008955080 modified "2023-10-04" @default.
• W2008955080 title "Pharmacological characterization of epinephrine-stimulated GTPase activity in human platelet membranes" @default.
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• W2008955080 doi "https://doi.org/10.1016/0006-2952(93)90644-c" @default.
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