期刊
JOURNAL OF PSYCHOPHARMACOLOGY
卷 29, 期 9, 页码 996-1012出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/0269881115586936
关键词
Imidazoline receptors; mouse and human brains; neuron and astrocyte cells; human platelets; treatments with I-1-and I-2-drugs in mice
资金
- Ministerio de Economia y Competitividad (MINECO) [SAF2011-29918]
- Fondo Europeo de Desarrollo Regional (FEDER), Spain
- Redes Tematicas de Investigacion Cooperativa en Salud-Red de Trastornos Adictivos (RETICS-RTA) [RD12/0028/0011]
- Instituto de Salud Carlos III (MINECO/FEDER), Spain
Various imidazoline receptor (IR) proteins have been proposed to mediate the effects of selective I-1- and I-2-IR drugs. However, the association of these IR-binding proteins with classic I-1- and I-2-radioligand binding sites remains somewhat controversial. In this study, three IR antibodies (anti-NISCH and anti-nischarin for I-1-IRs; and anti-IRBP for I-1/I-2-IRs) were used to immunodetect, characterize and compare IR protein patterns in brain (mouse and human; total homogenate, subcellular fractionation, grey and white matter) and some cell systems (neurones, astrocytes, human platelets). Various immunoreactive IRs (specific molecular weight bands coincidently detected with the different antibodies) were related to I-1- IR (167 kDa, 105/115 kDa and 85 kDa proteins) or I-2-IR (66 kDa, 45 kDa and 30 kDa proteins) types. The biochemical characterization of cortical 167 kDa protein, localized in the membrane/cytosol but not in the nucleus, indicated that this I-1-IR also forms part of higher order nischarin-related complexes. The contents of I-1-IR (167 kDa, 105/115 kDa, and 85 kDa) proteins in mouse brain cortex were upregulated by treatment with I-1-drugs (moxonidine, efaroxan) but not with I-2-drugs (BU-224, LSL 61122). Conversely, the contents of I-2-IR (66 kDa, 45 kDa and 30 kDa) proteins in mouse brain cortex were modulated by treatment with I-2-drugs (decreases after BU-224 and LSL 61122, and increases after idazoxan) but not with I-1-drugs (with the exception of moxonidine). These findings further indicate that brain immunoreactive IR proteins exist in multiple forms that can be grouped in the already known I-1- and I-2-IR types, which are expressed both in neurones and astrocytes.
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