Are high-affinity progesterone binding site(s) from porcine liver microsomes members of the σ receptor family?

Meyer, Christiane; Schmieding, Kerstin; Falkenstein, Elisabeth; Wehling, Martin

doi:10.1016/s0014-2999(98)00103-4

Cited by 38 publications

(18 citation statements)

References 25 publications

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“…The inhibition of ET-1 release caused by β-estradiol or progesterone is in agreement with other in vitro and in vivo studies (Meyer et al 1998;Ylikorkala et al 1995). However, in contrast to previously reported mechanisms, describing a steroid receptor-dependent signaling pathway, we found that female sex hormones depress the endothelial ET-1 secretion mainly via the involvement of sigma-1 receptors.…”

Section: Discussionsupporting

confidence: 92%

“…Recently, the cDNA of the mammalian sigma receptor subtype 1 has been cloned and high densities of this subtype has been found in steroid-producing tissues. This corresponds to the known ability of sigma-1 binding sites to interact with steroids such as progesterone or dehydroepiandrosterone as endogenous ligands of sigma receptors (Meyer et al 1998). Well-known exogenous ligands are ditolylguanidine (DTG) or haloperidol (Halo), a nonselective sigma-1 receptor antagonist.…”

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confidence: 99%

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Female Sex Hormones Decrease Constitutive Endothelin-1 Release via Endothelial Sigma-1/Cocaine Receptors: An Action Independent of the Steroid Hormone Receptors

et al. 2005

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Cardiovascular disease is rare in premenopausal women compared to men. The authors investigate sex hormone-induced endothelin-1 (ET-1) release and the involvement of classic sex hormone receptors as well as the ability of sigma-1/cocaine receptors to respond to sex hormones. ET-1 release was measured in the supernatant of endothelial cells after treatment with beta-estradiol, progesterone, testosterone, or combined with their antagonists, and with the sigma-1 receptor ligand ditolylguanidine (DTG), or haloperidol, a sigma-1 receptor antagonist. Binding assays were performed using 2.5 x 10(-8) M [3H]DTG. Female sex hormones decreased ET-1 release whereas testosterone increased it, sex hormone antagonists only slightly attenuated or had no effect on the respective hormone's effect. DTG totally blocked the female sex hormone-induced inhibition on ET-1 release, whereas testosterone-induced stimulation was not affected. However, haloperidol blocked both. [3H]DTG binding was displaced by beta -estradiol but not by testosterone. DTG-binding sites account for 513 +/- 114 per cell, KD 8.79 nM. These data suggest that besides classic steroid hormone receptors, sigma-1/cocaine receptors mediate the effects of female sex hormones on ET-1 release, an up to now unknown signalling pathway. Results also suggest that female and male sex hormones may bind to different sites on sigma-1 receptors, exerting opposite pharmacological effects.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Female Sex Hormones Decrease Constitutive Endothelin-1 Release via Endothelial Sigma-1/Cocaine Receptors: An Action Independent of the Steroid Hormone Receptors

et al. 2005

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“…The reason why PGRMC1-GFP does not form a dimer is unknown but could be due to the presence of GFP. Regardless, PGRMC1-GFP is capable of binding P4 through a single high-affinity binding site (Meyer et al 1998; Mansouri et al 2008; Peluso et al 2008; Peluso et al 2009) and increasing its level enhances the sensitivity of SIGCs to P4 (present study; Peluso et al 2006; Peluso et al 2008). These observations imply that P4 binds to PGRMC1-GFP within the cytoplasm and that this interaction is sufficient to enhance cell responsiveness to P4's anti-apoptotic action.…”

Section: Discussionmentioning

confidence: 63%

Progesterone inhibits apoptosis in part by PGRMC1-regulated gene expression

Peluso

Liu

Gawkowska

et al. 2010

Molecular and Cellular Endocrinology

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Progesterone Receptor Membrane Component-1 (PGRMC1) is present in both the cytoplasm and nucleus of spontaneously immortalized granulosa cells (SIGCs). PGRMC1 is detected as a monomer in the cytoplasm and a DTT-resistant PGRMC1 dimer in the nucleus. Transfected PGRMC1-GFP localizes mainly to the cytoplasm and does not form a DTT-resistant dimer. Moreover, forced expression of PGRMC1-GFP increases the sensitivity of the SIGCs to progesterone (P4) 's antiapoptotic action, indicating that the PGRMC1 monomer is functional. However, when endogenous PGRMC1 is depleted by siRNA treatment and replaced with PGRMC1-GFP, P4 responsiveness is not enhanced, although overall levels of PGRMC1 are increased. P4's anti-apoptotic action is also attenuated by actinomycin D, an inhibitor of RNA synthesis, and P4 activation of PGRMC1 suppresses Bad and increases Bcl2a1d expression. Taken together, the present studies suggest a genomic component to PGRMC1's anti-apoptotic mechanism of action, which requires the presence of the PGRMC1 dimer.

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“…Confirming these studies, other groups have shown that progesterone was indeed the neurosteroid which most potently inhibited the binding of 3 Poncelet et al (1993) several sigma-1 ligands in different preparations, such as the rat brain, splenocytes plasma membrane, and liver microsomes (Ross 1991;Klein and Musacchio 1994;Yamada et al 1994). However, many sigma-1 ligands (haloperidol, carbapentane, DTG, (+)-3-PPP, and rimcazole) inhibit the [ 3 H]-progesterone binding in rat liver preparations or porcine liver solubilized fractions Meyer et al 1998). Exogenous administration of neurosteroids leads to a dose-dependent inhibition of [ 3 H](+)-SKF 10,047 to sigma-1 receptors (Maurice et al 1996).…”

Section: Endogenous Ligands Of the Sigma Receptorsmentioning

confidence: 99%

Sigma receptors: biology and therapeutic potential

Guitart¹,

Codony²,

Monroy³

2004

Psychopharmacology

218

230

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More than 20 years after the identification of the sigma receptors as a unique binding site in the brain and in the peripheral organs, several questions regarding this receptor are still open. Only one of the subtypes of the receptor has been cloned to date, but the endogenous ligand still remains unknown, and the possible association of the receptor with a conventional second messenger system is controversial. From the very beginning, the sigma receptors were associated with various central nervous system disorders such as schizophrenia or movement disorders. Today, after hundreds of papers dealing with the importance of sigma receptors in brain function, it is widely accepted that sigma receptors represent a new and different avenue in the possible pharmacological treatment of several brain-related disorders. In this review, what is known about the biology of the sigma receptor regarding its putative structure and its distribution in the central nervous system is summarized first. The role of sigma receptors regulating cellular functions and other neurotransmitter systems is also addressed, as well as a short overview of the possible endogenous ligands. Finally, although no specific sigma ligand has reached the market, different pharmacological approaches to the alleviation and treatment of several central nervous system disorders and deficits, including schizophrenia, pain, memory deficits, etc., are discussed, with an overview of different compounds and their potential therapeutic use.

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Are high-affinity progesterone binding site(s) from porcine liver microsomes members of the σ receptor family?

Cited by 38 publications

References 25 publications

Female Sex Hormones Decrease Constitutive Endothelin-1 Release via Endothelial Sigma-1/Cocaine Receptors: An Action Independent of the Steroid Hormone Receptors

Female Sex Hormones Decrease Constitutive Endothelin-1 Release via Endothelial Sigma-1/Cocaine Receptors: An Action Independent of the Steroid Hormone Receptors

Progesterone inhibits apoptosis in part by PGRMC1-regulated gene expression

Sigma receptors: biology and therapeutic potential

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