Sastre-Coll A, Esteban S, Miralles A, Zanetti R, García-Sevilla J A
Laboratory of Neuropharmacology, Associate Unit of the Institute Cajal/CSIC, Department of Biology, University of the Balearic Islands, Cra. Valldemossa Km 7.5, E-07071, Palma de Mallorca, Spain.
Neurosci Lett. 2001 Mar 23;301(1):29-32. doi: 10.1016/s0304-3940(01)01599-3.
2-BFI (2-(2-benzofuranyl)-2-imidazoline) is a prototypical I2-imidazoline receptor ligand. In vivo, however, 2-BFI (1-20 mg/kg) decreased the synthesis of dopa/dopamine (DA) in rat striatum through mechanisms not related to interaction with I2-imidazoline receptors or to inhibition of the enzyme monoamine oxidase. The aim of this study was to unravel the mechanism underlying this potent effect of 2-BFI in brain. In vitro 2-BFI showed very low affinity for D2-dopamine receptors (K(i)=47 microM), and in vivo the drug (7 mg/kg) decreased the synthesis of striatal dopa/DA similarly in control rats (43%) and in rats pre-treated with alpha-methyl-para-tyrosine (50%) or cocaine (51%), indicating that this effect was not the result of D2-dopamine autoreceptor direct stimulation, inhibition of the enzyme tyrosine hydroxylase or blockade of neuronal DA reuptake. In DA-depleted (reserpine-treated) rats, however, 2-BFI did not inhibit significantly (11%), the synthesis of dopa/DA in the striatum, indicating that the effect of 2-BFI was indirectly mediated by endogenous DA through the activation of D2-dopamine autoreceptors. In conclusion, the I2-imidazoline receptor ligand 2-BFI is also a DA releasing agent in brain, and consequently a DA indirect agonist in vivo.
2-苯并呋喃咪唑（2-(2-苯并呋喃基)-2-咪唑啉）是一种典型的I2-咪唑啉受体配体。然而，在体内，2-苯并呋喃咪唑（1-20毫克/千克）通过与I2-咪唑啉受体相互作用无关或与抑制单胺氧化酶无关的机制，降低了大鼠纹状体中多巴/多巴胺（DA）的合成。本研究的目的是揭示2-苯并呋喃咪唑在脑中这种强效作用的潜在机制。在体外，2-苯并呋喃咪唑对D2-多巴胺受体的亲和力非常低（K(i)=47微摩尔），在体内，该药物（7毫克/千克）在对照大鼠（43%）以及用α-甲基-对-酪氨酸预处理的大鼠（50%）或可卡因处理的大鼠（51%）中，同样降低了纹状体中多巴/多巴胺的合成，这表明这种作用不是D2-多巴胺自身受体直接刺激、抑制酪氨酸羟化酶或阻断神经元多巴胺再摄取的结果。然而，在多巴胺耗竭（利血平处理）的大鼠中，2-苯并呋喃咪唑并没有显著抑制（11%）纹状体中多巴/多巴胺的合成，这表明2-苯并呋喃咪唑的作用是通过内源性多巴胺激活D2-多巴胺自身受体间接介导的。总之，I2-咪唑啉受体配体2-苯并呋喃咪唑在脑中也是一种多巴胺释放剂，因此在体内是一种多巴胺间接激动剂。
