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Steroid binding at sigma receptors: CNS and immunological implications
1National Institute on Drug Abuse, Addiction Research Centre, Baltimore, MD 21224.
Ciba Foundation Symposium
|January 1, 1990
Summary
Sigma receptors may mediate steroid-induced mental and immune changes. Steroid hormones, like progesterone, competitively inhibit sigma receptor binding, suggesting a shared molecular mechanism.
Area of Science:
- Neuroscience
- Endocrinology
- Immunology
Background:
- Sigma receptors are implicated in psychotomimetic effects of drugs like phencyclidine.
- Haloperidol and atypical antipsychotics are potent sigma receptor ligands.
- Sigma receptors are present in the central nervous system, immune, and endocrine systems.
Purpose of the Study:
- To investigate the interaction between steroid hormones and sigma receptors.
- To explore the potential role of sigma receptors in mediating steroid-induced effects.
Main Methods:
- Competitive binding assays using [3H] d-SKF-10,047 to assess steroid inhibition.
- Molecular modeling (geometric fitting, electrostatic potential calculations) to analyze structural similarities.
- Comparison of steroid affinities at sigma receptors with anti-inflammatory efficacy.
Main Results:
- Gonadal and adrenal steroids (progesterone, testosterone, deoxycorticosterone, corticosterone) competitively inhibited sigma receptor ligand binding.
- Molecular modeling indicated shared structural features between steroid hormones and sigma ligands, with the C-20 carbonyl oxygen as a potential pharmacophore.
- A qualitative correlation was observed between steroid affinities at sigma receptors and their anti-inflammatory effects.
Conclusions:
- Sigma receptors are distinct from classical progesterone receptors and are located in membrane fractions.
- Steroid hormones interact with sigma receptors, suggesting a role in mediating steroid-induced mental disturbances.
- Sigma receptor interactions with steroids may also influence immune function.