Analysis of information sources in references of the Wikipedia article "Octopamine" in English language version.
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{{cite journal}}: Cite uses deprecated parameter |citeseerx= (help)A recent study showed that TAAR1 mediates AMPH-induced activation of the downstreaming RhoA and cAMP signaling in HEK293 cells expressing DAT but not cells without DAT (Underhill et al. 2019). Interestingly, two different G proteins G13 and Gs regulated TAAR1 activation (Underhill et al. 2019). It was further shown that AMPH induced activation of both TAAR1-G13-RhoA and TAAR1-Gs-PKA signaling were dependent on DAT (Underhill et al. 2019). However, the TAAR1 agonist octopamine, which is not a substrate of DAT, did not activate RhoA signaling. Accordingly, it was suggested that these TAAR1/RhoA and TAAR1/PKA signaling pathways might be particular cascades that mediate the effects of amphetamines and could not generalize to other TAAR1 agonists (Underhill et al. 2019).
Notably, the TAAR1 agonist octopamine (10 μM) did not activate RhoA in these cells (Fig. 1c). Octopamine is a potent activator of TAAR1 [4, 5] however, it is a poor substrate for DAT [23]. Because the DAT dependence of the effects of TAAR1 agonists on RhoA activation suggests that TAAR1 agonists act intracellularly to stimulate the receptor, we permeablized the HEK293 cells with streptolysin O to allow octopamine access to the cytoplasm [24]. In the presence of streptolysin O, octopamine produces an approximately twofold increase in activated Rho, whereas streptolysin O had no effect on its own, demonstrating that a TAAR1 agonist that is not a substrate for DAT can activate Rho-dependent signaling once it enters the cell. These studies also imply that entry through the DAT may not be prerequisite for activation of intracellular signaling by TAAR1; in fact, two recently-developed compounds from Roche (RO5166017 and RO5203648) show TAAR1 agonist activity in DAT KO mice and thus may gain access to the cell interior via other avenues [25, 26].
{{cite journal}}: Cite uses deprecated parameter |citeseerx= (help)A recent study showed that TAAR1 mediates AMPH-induced activation of the downstreaming RhoA and cAMP signaling in HEK293 cells expressing DAT but not cells without DAT (Underhill et al. 2019). Interestingly, two different G proteins G13 and Gs regulated TAAR1 activation (Underhill et al. 2019). It was further shown that AMPH induced activation of both TAAR1-G13-RhoA and TAAR1-Gs-PKA signaling were dependent on DAT (Underhill et al. 2019). However, the TAAR1 agonist octopamine, which is not a substrate of DAT, did not activate RhoA signaling. Accordingly, it was suggested that these TAAR1/RhoA and TAAR1/PKA signaling pathways might be particular cascades that mediate the effects of amphetamines and could not generalize to other TAAR1 agonists (Underhill et al. 2019).
Notably, the TAAR1 agonist octopamine (10 μM) did not activate RhoA in these cells (Fig. 1c). Octopamine is a potent activator of TAAR1 [4, 5] however, it is a poor substrate for DAT [23]. Because the DAT dependence of the effects of TAAR1 agonists on RhoA activation suggests that TAAR1 agonists act intracellularly to stimulate the receptor, we permeablized the HEK293 cells with streptolysin O to allow octopamine access to the cytoplasm [24]. In the presence of streptolysin O, octopamine produces an approximately twofold increase in activated Rho, whereas streptolysin O had no effect on its own, demonstrating that a TAAR1 agonist that is not a substrate for DAT can activate Rho-dependent signaling once it enters the cell. These studies also imply that entry through the DAT may not be prerequisite for activation of intracellular signaling by TAAR1; in fact, two recently-developed compounds from Roche (RO5166017 and RO5203648) show TAAR1 agonist activity in DAT KO mice and thus may gain access to the cell interior via other avenues [25, 26].
A recent study showed that TAAR1 mediates AMPH-induced activation of the downstreaming RhoA and cAMP signaling in HEK293 cells expressing DAT but not cells without DAT (Underhill et al. 2019). Interestingly, two different G proteins G13 and Gs regulated TAAR1 activation (Underhill et al. 2019). It was further shown that AMPH induced activation of both TAAR1-G13-RhoA and TAAR1-Gs-PKA signaling were dependent on DAT (Underhill et al. 2019). However, the TAAR1 agonist octopamine, which is not a substrate of DAT, did not activate RhoA signaling. Accordingly, it was suggested that these TAAR1/RhoA and TAAR1/PKA signaling pathways might be particular cascades that mediate the effects of amphetamines and could not generalize to other TAAR1 agonists (Underhill et al. 2019).
Notably, the TAAR1 agonist octopamine (10 μM) did not activate RhoA in these cells (Fig. 1c). Octopamine is a potent activator of TAAR1 [4, 5] however, it is a poor substrate for DAT [23]. Because the DAT dependence of the effects of TAAR1 agonists on RhoA activation suggests that TAAR1 agonists act intracellularly to stimulate the receptor, we permeablized the HEK293 cells with streptolysin O to allow octopamine access to the cytoplasm [24]. In the presence of streptolysin O, octopamine produces an approximately twofold increase in activated Rho, whereas streptolysin O had no effect on its own, demonstrating that a TAAR1 agonist that is not a substrate for DAT can activate Rho-dependent signaling once it enters the cell. These studies also imply that entry through the DAT may not be prerequisite for activation of intracellular signaling by TAAR1; in fact, two recently-developed compounds from Roche (RO5166017 and RO5203648) show TAAR1 agonist activity in DAT KO mice and thus may gain access to the cell interior via other avenues [25, 26].
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