Epinephrine Activates Both Gs and Gi Pathways, but Norepinephrine Activates Only the Gs Pathway through Human β2-Adrenoceptors Overexpressed in Mouse Heart
作者： Jürgen F. Heubach , Ursula Ravens , Alberto J. Kaumann
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摘要: Isoproterenol increases and decreases contractile force at low high concentrations, respectively, through β2-adrenoceptors overexpressed in transgenic mouse heart (TG4), consistent with activation of both Gs Gi proteins. Using TG4 hearts, we demonstrated that epinephrine behaves like isoproterenol, but norepinephrine does not. Epinephrine increased (-log EC50M = 9.4) decreased 6.5) left atrial force. Pertussis toxin (PTX) abolished the negative inotropic effects epinephrine, mediation protein. Norepinephrine only 7.5). (10-100 μM) prevented positive hardly affected epinephrine. Cardiodepressive concentrations (1-10 antagonized norepinephrine. In free wall right ventricle, caused effects, PTX-sensitive as observed atrium. (10 nM), a concentration causing maximum increase force, (1 100 cAMP-dependent protein kinase activity ventricle. did not activity. The results were simulated model two β2-adrenoceptor sites. For one site involved receptor coupling to Gs, compete. other site, recognized by norepinephrine, leads coupling.
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