| Glu regulation: regulates excitotoxic effect of Glu. two subtypes of σ1R may affect differentially the Glu-mediated NMDA neurotransmission in the terminal and origin regions of the mesolimbic and nigrostriatal DA-ergic systems. Functional interaction between σ2R and NMDARs in the hippocampus. σ1R agonist may protect neurons by mechanism involving anti-apototic protein bcl-2 |
CNS |
(27,360,386,417,425,447,450,451, 769,770,775,786–788) |
| Regulation of Mn2+, Hg2+ and Pb2+ neurotoxicity |
CNS |
(379) |
| σ1R initiates neurite outgrowth and sprouting. σ1R agonist potentiates nerite-sprouting by nerve growth factor. σ1R agonist may potentiate effects of BDNF and EGF |
CNS |
(32,41,164,176,177,185,803) |
| Regulation of Ca2+ or K+ signaling. Interacts with VDCC’s. Modulate Glu and 5-HT transmissions. |
CNS |
(88,133,138,139,153,154,161,164--166, 181,249–251,377,821,829) |
| σ1R ligands affect iGluR subunit levels of mRNA and protein, differentially regulating levels of NMDA2A and GluR2 in a regionally specific manner. |
Frontoparietal cortex, cingulated cortex, dorsal striatum, nucleus accumbens |
(15,380,802) |
| Activation of spinal σ1R enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NMDA receptor NR1 subunit |
CNS |
(458,483,681,881–883,894) |
| Agonist of σ1R and σ2R inhibit NMDA-stimulated DA release from motor and limbic areas of rat brain. |
CNS |
(896) |
| Cardiac excitation and rhythmic control |
Parasympathetic intracardiac neurons, hERG channel |
(756,919–922) |
| Effects of σ1R mediated via PKC- and PKA dependent phosphorylation of the NMDA receptor, altered Na+ channels |
Heart and vessels |
(150,458,928,929) |
| σR ligands modulate contractility, Ca2+ influx and cardiac rate. σR activation prevent reperfusion contracture, increases pressure in left ventricle and improves survival of cardiac myocytes after ischemia and reperfusion. Activation of σR reversibly blocks the delay in outwardly rectifying K+ channels, conductance Ca2+ sensitive K+ channels and the M-current. |
Heart |
(923,930–932) |
| σR agonist increase intracellular Ca2+ levels by stimulating IP3 production, modulating contractility |
Peripheral arteries |
(167) |
| Ca2+ influx |
Muscle |
(764,938) |
| Act in conjunction with GluRs to affect cellular changes |
Osteoblasts, osteocytes, osteoclasts |
(492,497,943–948) |
| Modulate ion channels |
Lungs |
(194,440,733,959–961) |
| Regulatory functions. Control of pituitary functions. Antidiuretic hormone release. Inhibit K+ channel function. |
Endocrine system, pituitary |
(127,222,868,962,968) |
| May affect their signaling pathways in conjunction with PROG or prostaglandin E1.
|
Spermatozoa |
(976,977) |
| Modulation of ion channels. Forms a immunoprecipitating complex with ion channels |
Xenopus oocytes, neurohypophysis |
(88) |
| Neuroprotection against ganglion Glu toxicity, apoptosis, σ1R and σ2R binding activity stimulated during oxidative stress, important during lens development |
Eye – retinal ganglion cells, inner nuclear membrane, inner segments of the photoreceptors, retinal pigment epithelial cells, retinal Mueller cells |
(74,783,913,987,989–991,994,995) |
| Regulation of ileal contractions, may be involved in regulating acid secretion in stomach |
Myenteric plexus of the guinea pig ileum |
(314,747,998,999) |
| Inhibit electrically or 5-HT-evoked contractions, stimulation of salivary secretion |
Gastrointestinal longitudinal muscle and myenteric plexus |
(314,1001) |
| 5-HT transmissions. |
Vagus |
(1002–1005) |
| σ2Rs inhibit lymphocyte activation. Potent immunoregulatory properties including induction of IL-10, suppression if IFN-γ and suppression of granulocyte colony stimulating factor. |
Human peripheral blood mononuclear cells, lymphocytes |
(98,677,1010–1014) |
| Lymphocyte proliferation, miogen-induced IgG and IgM production, LPS-induced IL-I production |
Splenocytes |
(98,1020) |
