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Methcathinone decreases dopamine transporter function: Role of protein kinase C
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2021-07-28 , DOI: 10.1111/jnc.15483 Charlotte P Magee 1, 2 , BaoMinh D Le 2 , Yasmeen H Siripathane 2 , Diana G Wilkins 3 , Glen R Hanson 1, 2 , Annette E Fleckenstein 1, 2
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2021-07-28 , DOI: 10.1111/jnc.15483 Charlotte P Magee 1, 2 , BaoMinh D Le 2 , Yasmeen H Siripathane 2 , Diana G Wilkins 3 , Glen R Hanson 1, 2 , Annette E Fleckenstein 1, 2
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Methcathinone (MCAT) is a psychostimulant of abuse that can cause both persistent striatal dopaminergic and serotonergic, as well as hippocampal serotonergic, deficits. Evidence suggests that the rapid effects of stimulants that are structurally and mechanistically similar to MCAT on monoamine transporter function may contribute to the abuse liability and/or persistent monoaminergic deficits caused by these agents. Thus, effects of MCAT on 1) striatal dopamine (DA) transporter (DAT); and 2) striatal and hippocampal serotonin transporter (SERT) function, as determined in tissues from adult male rats, were assessed. As reported previously, a single administration of MCAT rapidly (within 1 hr) decreases striatal [3H]DA uptake. Similarly, incubation of rat synaptosomes with MCAT at 37℃ (but not 4˚C) decreased striatal [3H]DA uptake. Incubation with MCAT likewise decreased [3H]5HT but not vesicular [3H]DA uptake. MCAT incubation in vitro was without effect on [3H]DA uptake in striatal synaptosomes prepared from MCAT-treated rats. The decrease in [3H]DA uptake caused by MCAT incubation: (a) reflected a decrease in Vmax, with minimal change in Km, and (b) was attenuated by co-incubation with the cell-permeable calcium chelator, N,N'-[1,2-ethanediylbis(oxy-2,1-phenylene)]bis[N-[2-[(acetyloxy)methoxy]-2-oxoethyl]-1,1'-bis[(acetyloxy)methyl] ester-glycine (BAPTA-AM), as well as the non-selective protein kinase-C (PKC) inhibitors bisindolylmaleimide-1 (BIM-1) and 2-[1-3(Aminopropyl)indol-3-yl]-3(1-methyl-1H-indol-3-yl)maleimide (or Bisindolylmaleimide VIII; Ro-31-7549). Taken together, these results suggest that in vitro MCAT incubation may model important aspects of MCAT administration in vivo, and that calcium and PKC contribute to the in vitro effects of MCAT on DAT.
中文翻译：
甲卡西酮降低多巴胺转运蛋白功能：蛋白激酶 C 的作用
Methcathinone (MCAT) is a psychostimulant of abuse that can cause both persistent striatal dopaminergic and serotonergic, as well as hippocampal serotonergic, deficits. Evidence suggests that the rapid effects of stimulants that are structurally and mechanistically similar to MCAT on monoamine transporter function may contribute to the abuse liability and/or persistent monoaminergic deficits caused by these agents. Thus, effects of MCAT on 1) striatal dopamine (DA) transporter (DAT); and 2) striatal and hippocampal serotonin transporter (SERT) function, as determined in tissues from adult male rats, were assessed. As reported previously, a single administration of MCAT rapidly (within 1 hr) decreases striatal [3H]DA uptake. Similarly, incubation of rat synaptosomes with MCAT at 37℃ (but not 4˚C) decreased striatal [3H]DA uptake. Incubation with MCAT likewise decreased [3H]5HT but not vesicular [3H]DA uptake. MCAT incubation in vitro was without effect on [3H]DA uptake in striatal synaptosomes prepared from MCAT-treated rats. The decrease in [3H]DA uptake caused by MCAT incubation: (a) reflected a decrease in Vmax, with minimal change in Km, and (b) was attenuated by co-incubation with the cell-permeable calcium chelator, N,N'-[1,2-ethanediylbis(oxy-2,1-phenylene)]bis[N-[2-[(乙酰氧基)甲氧基]-2-氧乙基]-1,1'-双[(乙酰氧基)甲基]酯-甘氨酸 (BAPTA-AM)，以及非选择性蛋白激酶-C (PKC ) 抑制剂双吲哚基马来酰亚胺-1 (BIM-1) 和 2-[1-3(氨基丙基)indol-3-yl]-3(1-methyl-1H-indol-3-yl)maleimide（或 Bisindolylmaleimide VIII; Ro-31 -7549）。综上所述，这些结果表明，体外 MCAT 孵育可以模拟体内 MCAT 给药的重要方面，并且钙和 PKC 有助于 MCAT 对 DAT 的体外影响。
更新日期：2021-09-29
中文翻译：
甲卡西酮降低多巴胺转运蛋白功能：蛋白激酶 C 的作用
Methcathinone (MCAT) is a psychostimulant of abuse that can cause both persistent striatal dopaminergic and serotonergic, as well as hippocampal serotonergic, deficits. Evidence suggests that the rapid effects of stimulants that are structurally and mechanistically similar to MCAT on monoamine transporter function may contribute to the abuse liability and/or persistent monoaminergic deficits caused by these agents. Thus, effects of MCAT on 1) striatal dopamine (DA) transporter (DAT); and 2) striatal and hippocampal serotonin transporter (SERT) function, as determined in tissues from adult male rats, were assessed. As reported previously, a single administration of MCAT rapidly (within 1 hr) decreases striatal [3H]DA uptake. Similarly, incubation of rat synaptosomes with MCAT at 37℃ (but not 4˚C) decreased striatal [3H]DA uptake. Incubation with MCAT likewise decreased [3H]5HT but not vesicular [3H]DA uptake. MCAT incubation in vitro was without effect on [3H]DA uptake in striatal synaptosomes prepared from MCAT-treated rats. The decrease in [3H]DA uptake caused by MCAT incubation: (a) reflected a decrease in Vmax, with minimal change in Km, and (b) was attenuated by co-incubation with the cell-permeable calcium chelator, N,N'-[1,2-ethanediylbis(oxy-2,1-phenylene)]bis[N-[2-[(乙酰氧基)甲氧基]-2-氧乙基]-1,1'-双[(乙酰氧基)甲基]酯-甘氨酸 (BAPTA-AM)，以及非选择性蛋白激酶-C (PKC ) 抑制剂双吲哚基马来酰亚胺-1 (BIM-1) 和 2-[1-3(氨基丙基)indol-3-yl]-3(1-methyl-1H-indol-3-yl)maleimide（或 Bisindolylmaleimide VIII; Ro-31 -7549）。综上所述，这些结果表明，体外 MCAT 孵育可以模拟体内 MCAT 给药的重要方面，并且钙和 PKC 有助于 MCAT 对 DAT 的体外影响。
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