期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1803, 期 12, 页码 1396-1408出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2010.08.005
关键词
Sigma-1 receptors; Synaptosomes; Prelimbic cortex; D1 receptors; cAMP-dependent protein kinase; Ca2+ concentration
资金
- Foundation of National Natural Science of China [31070932, 30900424, 30670653, 30821002]
- Ministry of Science and Technology of China [2009CB52201]
- Shanghai Leading Academic Discipline
Sigma-1 receptors are highly expressed in the brain. The downstream signaling mechanisms associated with the sigma-1 receptor activation have been shown to involve the activation of protein kinase C (PKC), the control of Ca-2 homoeostasis and the regulation of voltage- and ligand-gated ion channels. But few studies examined the regulatory effect of sigma-1 receptors on metabotropic receptor signaling. The present paper studied the regulatory effect of sigma-1 receptors on the signaling of dopamine D1 receptors, one of metabotropic receptors, by examining the effect of sigma-1 receptor agonists on the D1 receptor agonist-induced cAMP-dependent protein kinase (PKA) activation at presynaptic sites using the synaptosomes from the prelimbic cortex. The results showed that sigma-1 receptor agonists alone had no effects on the PKA activity, but could amplify the D1 receptor agonist-induced PKA activation. The sigma-1 receptor agonist also amplified the membrane-permeable analog of cAMP- and the adenylyl cyclase (AC) activator-induced PKA activation, but did not on the D1 receptor agonist-induced AC activation. The conventional PKC (cPKC), especially the PKC beta 1, and the extracellular Ca2+ influx through L-type Ca2+ channels might play key roles in the amplifying effect of the sigma-1 receptor agonists. The activation of PKC by sigma-1 receptor agonists was the upstream event of the increase in the intrasynaptosomal Ca2+ concentration. These results suggest that sigma-1 receptors may amplify the D1 receptor agonist-induced PKA activation by sigma-1 receptors - cPKC (especially the PKC beta 1) - L-type Ca2+ channels - Ca2+ - AC and/or cAMP signaling pathway. (C) 2010 Elsevier RV. All rights reserved.
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