Shores M M, Szot P, Veith R C
Geriatric Research, Education and Clinical Center (GRECC), Veterans Affairs Medical Center, Seattle, WA 98108.
Brain Res Mol Brain Res. 1994 Dec;27(2):337-41. doi: 10.1016/0169-328x(94)90020-5.
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.
对接受短期（2天）治疗的大鼠进行去甲肾上腺素转运体（NET）的原位杂交，这些大鼠分别用α-2受体激动剂（可乐定）或拮抗剂（育亨宾）治疗，随后给予生理盐水或地昔帕明（DMI）。“生理盐水”组腹腔注射可乐定、育亨宾或生理盐水，随后注射生理盐水。“DMI”组腹腔注射可乐定、育亨宾或生理盐水，随后注射DMI。给药剂量分别为可乐定（0.10mg/kg）、育亨宾（0.5mg/kg）和DMI（10mg/kg）。在“生理盐水”组中，与生理盐水/生理盐水组动物相比，可乐定/生理盐水组动物的NET mRNA表达显著降低。在“DMI”组中，与生理盐水/DMI组动物相比，可乐定/DMI组动物中观察到DMI诱导的NET mRNA增加有所减弱。在两个治疗组中，与相应的对照动物相比，给予育亨宾并未改变NET mRNA的表达。这些发现表明，DMI诱导的NET mRNA增加不是通过α-2受体介导的，因为尽管可乐定减弱了DMI的作用，但α-2拮抗剂育亨宾并没有产生相反的增强作用。可乐定对DMI作用的减弱可能是通过咪唑受体发生的，因为可乐定是咪唑受体的激动剂，但育亨宾在该受体上没有已知活性。需要进一步的研究来阐明DMI诱导的NET mRNA增加的机制，并将NET mRNA的变化与突触膜上转运体的表达相关联。
