| CNS: corpus striatum, nucleus accumbens |
|
(61) |
| Brain: substantia nigra, pars compacta |
|
(656) |
| CNS: dentate gyrus of hippocampus, facial nucleus, thalamic, hypothalamic nucei, straitum, cerebellum dorsal raphe nucleus and locus coeruleus |
|
(171,765,766,302) |
| Hippocampal pyramidal cell layer, hypothalamus, central grey and red nucleus, pontine, cranial nerve nuclei, pontine nuclei, Pons – medulla, spinal cord – ventral and dorsal route ganglia |
|
(761) |
| Brain: cortex limbic area amygdala |
|
(762) |
| Brain: cerebellum |
|
(763) |
| Brain: Medulla – pons, midbrain, cerebellum, thalamus, straitum, cortex, hippocampus |
|
(78,79) |
| Brain: cerebral cortex, straitum, hippocampus, cerebellum |
|
(767) |
| Brain: substantia nigra, central grey matter, oculomotor nuclei, cerebellum, nucleus accumbens, amygdale, olfactory bulb, hippocampus, motor cortex |
|
(766,768) |
| CNS |
Glu regulation, regulates excitotoxic effect of Glu |
(386,417,425,447,450,451, 769,770,775,) |
| CNS |
Regulation of Mn2+, Hg2+ and Pb2+ neurotoxicity. |
(379) |
| Neurons: ependymocytes, oligodendrocytes and peripheral nervous system Schwann cells |
|
(171,672,771–773) |
| CNS |
σ1R agonist are antiamnesic, improve cognitive abilities |
(27,181,212,365,376,602,753, 776–781,783,785) |
| CNS |
Neuroprotection – 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. Also, functional interaction between σ2R and NMDARs in the hippocampus. σ1R agonist may protect neurons by mechanism involving anti-apototic protein bcl-2. |
(360,786–788, ) |
| CNS |
σ1R initiates neurite outgrowth and sprouting. σ1R agonist potentiates neurite-sprouting by nerve growth factor. σ1R agonist may potentiate effects of BDNF and EGF |
(32,41,164,176,177,185,803) |
| CNS |
Mechanism of action of σR ligands in depression – regulation of Ca2+ or K+ signaling. Interacts with VDCC’s. Modulate Glu and 5-HT transmissions. May be a target for serotonin reuptake inhibitors. |
(88,133,139,153,161,164–166,181,249–251, 376,377,664,828, 829) |
| Brain: frontoparietal cortex, cingulated cortex, dorsal striatum, nucleus accumbens |
σ1R ligands affect iGluR subunit levels of mRNA and protein, differentially regulating levels of NMDA2A and GluR2 in a regionally specific manner. |
(15,380,802) |
| CNS |
Activation of σ1Rs antagonize opioid analgesia whereas antagonists potentiate opioid analgesia. Excitatory amino acids have actions on σRs indicating action via the Glu system. Activation of spinal σ1R enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NMDA receptor NR1 subunit |
(458,483,681,881–883,894) |
| CNS |
Agonist of σ1R and σ2R inhibit NMDA-stimulated DA release from motor and limbic areas of rat brain. |
(896) |
| ANS: Parasympathetic intracardiac neurons |
Cardiac excitation and rhythmic control |
(756,920–922) |
| Ion Channel: hERG channel |
Cardiac excitation and rhythmic control |
(919–922) |
| Heart and vessels |
Effects of σ1R mediated via PKC- and PKA dependent phosphorylation of the NMDA receptor, altered Na+ channels |
(150,458,928,929) |
| Heart |
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. |
(923,930–932) |
| Peripheral arteries |
σR agonist increase intracellular Ca2+ levels by stimulating IP3 production, modulating contractility. |
(167) |
| Muscle |
Dystonia |
(764,938) |
| Osteoblasts |
Act in conjunction with GluRs to affect cellular changes |
(943,944) |
| Osteocytes, osteoclasts |
Act in conjunction with GluRs to affect cellular changes |
(492,497,765,945–947) |
| Lung: pulmonary nerves |
|
(951) |
| Larynx, esophagus, mast cells |
|
(516,957,958) |
| Airway passage |
Excitation of GluRs may be important in airway inflammation and hyper reactivity observed in bronchial asthma |
(440,959,960) |
| Airways |
Antitussive |
(194,733,961) |
| Pituitary, adrenal, testis and ovary |
|
(676) |
| Endocrine system |
Regulatory functions |
(127,222,962) |
| Pituitary |
Control of pituitary functions |
(868) |
| Endocrine system |
Antidiuretic hormone release |
(968) |
| Posterior pituitary |
Inhibit K+ channel function |
(138,139) |
| Placenta |
|
(976) |
| Spermatozoa |
May affect signaling pathways in conjunction with PROG or prostaglandin E1.
|
(976,977) |
| Ovary – follicles |
|
(676) |
| Testis: ductuli efferentes, ductus epididymis, seminiferous tubules |
|
(676) |
| Xenopus oocytes, neurohypophysis |
Modulation of ion channels. Forms a immunoprecipitating complex with ion channels |
(88) |
| Liver, localized to lipid rafts in rat liver phospholipid membranes, mitochondria |
|
(92,113,980–983) |
| Kidney |
|
(92) |
| Eye: retinal ganglion cells, inner nuclear membrane, inner segments of the photoreceptors, retinal pigment epithelial cells, retinal Mueller cells, |
Neuroprotection against ganglion Glu toxicity, apoptosis, σ1R and σ2R binding activity stimulated during oxidative stress, important during lens development |
(74,783,913,987,989–991,994,995) |
| Myenteric plexus of the guinea pig ileum |
Regulation of ileal contractions, may be involved in regulating acid secretion in stomach |
(314,747,998,999) |
| Gastrointestinal longitudinal muscle and myenteric plexus |
Inhibit electrically or 5-HT-evoked contractions, stimulation of salivary secretion |
(314,1001) |
| Vagus |
Induce emesis |
(1002–1005) |
| Human peripheral blood mononuclear cells, lymphocytes |
σ2Rs inhibit lymphocyte activation. Potent immunoregulatory properties including induction of IL-10, suppression of IFN-γ and suppression of granulocyte colony stimulating factor. |
(98,677,1010–1014) |
| Splenocytes |
Lymphocyte proliferation, mitogen-induced IgG and IgM production, LPS-induced IL-I production |
(98,1020) |
| Viral RNA |
Regulate early steps in viral RNA replication |
(1017,1018) |
| Host antitumor immunity |
σR-dependent cytokine modulation. Ligand can induce apoptosis by changes in cytosolic Ca2+, ceramide and sphingolipid concentrations. |
(1019,1013) |
| Neoplasia |
Receptors overexpressed in many cancer tissues |
(1022,1023) |
