Desipramine-induced increase in norepinephrine transporter mRNA is not mediated via alpha 2 receptors.
In situ hybridization for the norepinephrine transporter (NET) was performed in rats receiving short-term (2 days) treatment with either an alpha-2 (alpha 2) receptor agonist (clonidine) or antagonist (yohimbine) followed by saline or desipramine (DMI). The 'saline' group received intraperitoneal injections of either clonidine, yohimbine or saline followed by an injection of saline. The 'DMI' group received intraperitoneal injections of either clonidine, yohimbine or saline followed by an injection of DMI. Dosages given were clonidine (0.10 mg/kg), yohimbine (0.5 mg/kg) and DMI (10 mg/kg). In the 'saline' group, the clonidine/saline animals had significantly less NET mRNA expression compared to the saline/saline animals. In the 'DMI' group an attentuation of the DMI-induced increase in NET mRNA was observed in the clonidine/DMI animals compared to the saline/DMI animals. In both treatment groups, administration of yohimbine did not alter the expression of NET mRNA compared to the appropriate control animals. These findings suggest that the DMI-induced increase in NET mRNA is not mediated via alpha 2 receptors for, although clonidine attenuates DMI's effect, there is no reciprocal enhancement with the alpha 2 antagonist yohimbine. Clonidine's attenuation of DMI's effect may occur via the imidazole receptor as clonidine is an agonist at the imidazole receptor but yohimbine has no known activity at it. Additional studies are needed to clarify the mechanism of the DMI-induced increase in NET mRNA and to correlate changes in NET mRNA with transporter expression at the synaptic membrane.
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Geriatric Research, Education and Clinical Center (GRECC), Veterans Affairs Medical Center, Seattle, WA 98108.
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D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000235:genetics*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2; D027981:Symporters; D015016:Yohimbine / Q000494:pharmacology
D002352:Carrier Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; C493226:Slc6a2 protein, rat; D027981:Symporters; D015016:Yohimbine; D003000:Clonidine; D003891:Desipramine; D009638:Norepinephrine