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Inhibitory effects of clozapine and other antipsychotic drugs on noradrenaline transporter in cultured bovine adrenal medullary cells.

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Title: Inhibitory effects of clozapine and other antipsychotic drugs on noradrenaline transporter in cultured bovine adrenal medullary cells.
Authors: Yoshimura, R., Yanagihara, N., Hara, K., Terao, T., Nakamura, J., Ueno, S., Toyohira, Y., Uezono, Y., Kaneko, S., Kawamura, M., Abe, K., Izumi, F.
Source: Psychopharmacology. 2000, Vol. 149 Issue 1, p17. 7p.
Subjects: Clozapine, Antipsychotic agents, Adrenal medulla, Noradrenaline, Physiology
Abstract: Abstract The effects of clozapine and other antipsychotic drugs on noradrenaline (NA) transport were examined in cultured bovine adrenal medullary cells and in transfected Xenopus laevis oocytes expressing the bovine NA transporter. Incubation of adrenal medullary cells with clozapine (30-1000 ng/ml) inhibited desipramine (DMI)-sensitive uptake of [[sup 3]H]NA in a concentration-dependent manner (IC[sub 50]=110 ng/ml or 336 nM). Other antipsychotic drugs such as haloperidol, chlorpromazine, and risperidone also decreased [[sup 3]H]NA uptake (IC[sub 50]= 144, 220, and 210 ng/ml or 383, 690, and 512 nM, respectively). Eadie-Hofstee analysis showed that clozapine reduced V[sub max] of uptake of [[sup 3]H]NA and increased K[sub m]. Furthermore, clozapine inhibited specific binding of [[sup 3]H]DMI to plasma membranes isolated from bovine adrenal medulla (IC[sub 50]=48 ng/ml or 146 nM). Scatchard plot analysis of [[sup 3]H]DMI binding revealed that clozapine decreased both B[sub max] and K[sub d]. Other antipsychotic drugs, including haloperidol, chlorpromazine, and risperidone, also reduced [[sup 3]H]DMI binding to the membranes. In transfccted Xenopus oocytes expressing the bovine NA transporter, clozapine inhibited [[sup 3]H]NA uptake in a concentration-dependent manner similar to that observed in adrenal medullary cells. These results suggest that clozapine and haloperidol directly inhibit transport of NA by acting on the site of an NA transporter that influences both substrate transport and binding of tricyclic antidepressants. [ABSTRACT FROM AUTHOR]
Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Inhibitory effects of clozapine and other antipsychotic drugs on noradrenaline transporter in cultured bovine adrenal medullary cells.
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  Data: <searchLink fieldCode="AR" term="%22Yoshimura%2C+R%2E%22">Yoshimura, R.</searchLink><br /><searchLink fieldCode="AR" term="%22Yanagihara%2C+N%2E%22">Yanagihara, N.</searchLink><br /><searchLink fieldCode="AR" term="%22Hara%2C+K%2E%22">Hara, K.</searchLink><br /><searchLink fieldCode="AR" term="%22Terao%2C+T%2E%22">Terao, T.</searchLink><br /><searchLink fieldCode="AR" term="%22Nakamura%2C+J%2E%22">Nakamura, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Ueno%2C+S%2E%22">Ueno, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Toyohira%2C+Y%2E%22">Toyohira, Y.</searchLink><br /><searchLink fieldCode="AR" term="%22Uezono%2C+Y%2E%22">Uezono, Y.</searchLink><br /><searchLink fieldCode="AR" term="%22Kaneko%2C+S%2E%22">Kaneko, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Kawamura%2C+M%2E%22">Kawamura, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Abe%2C+K%2E%22">Abe, K.</searchLink><br /><searchLink fieldCode="AR" term="%22Izumi%2C+F%2E%22">Izumi, F.</searchLink>
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  Data: Abstract The effects of clozapine and other antipsychotic drugs on noradrenaline (NA) transport were examined in cultured bovine adrenal medullary cells and in transfected Xenopus laevis oocytes expressing the bovine NA transporter. Incubation of adrenal medullary cells with clozapine (30-1000 ng/ml) inhibited desipramine (DMI)-sensitive uptake of [[sup 3]H]NA in a concentration-dependent manner (IC[sub 50]=110 ng/ml or 336 nM). Other antipsychotic drugs such as haloperidol, chlorpromazine, and risperidone also decreased [[sup 3]H]NA uptake (IC[sub 50]= 144, 220, and 210 ng/ml or 383, 690, and 512 nM, respectively). Eadie-Hofstee analysis showed that clozapine reduced V[sub max] of uptake of [[sup 3]H]NA and increased K[sub m]. Furthermore, clozapine inhibited specific binding of [[sup 3]H]DMI to plasma membranes isolated from bovine adrenal medulla (IC[sub 50]=48 ng/ml or 146 nM). Scatchard plot analysis of [[sup 3]H]DMI binding revealed that clozapine decreased both B[sub max] and K[sub d]. Other antipsychotic drugs, including haloperidol, chlorpromazine, and risperidone, also reduced [[sup 3]H]DMI binding to the membranes. In transfccted Xenopus oocytes expressing the bovine NA transporter, clozapine inhibited [[sup 3]H]NA uptake in a concentration-dependent manner similar to that observed in adrenal medullary cells. These results suggest that clozapine and haloperidol directly inhibit transport of NA by acting on the site of an NA transporter that influences both substrate transport and binding of tricyclic antidepressants. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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