Title

Evidence that the σ1 receptor is not directly coupled to G proteins

Document Type

Journal Article

Publication Date

11-17-2000

Journal

European Journal of Pharmacology

Volume

408

Issue

2

DOI

10.1016/S0014-2999(00)00774-3

Keywords

σ Receptor; (+)Pentazocine; [ S]GTPγS autoradiography 35; Cerebellum; GTPase; Haloperidol

Abstract

Sigma (σ) receptors have been implicated in psychosis, cognition, neuroprotection, and locomotion in the central nervous system. The signal transduction mechanisms for σ receptors have not been fully elucidated. In this study, we examined the possible coupling between σ1 receptors and heterotrimeric guanine nucleotide-binding proteins (G proteins) in rodent brain. In σ1 receptor-rich cerebellar membrane preparations, the competitive binding curves of two σ1 agonists, (+)pentazocine and 1S,2R-(-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrro lidinyl)cyclohexylamine (BD737), were unaffected by the addition of 10 μM guanosine-5'-O-(γ-thio)-triphosphate (GTPγS). Neither (+)pentazocine (1-100 μM) nor BD737 (0.01-10 μM) stimulated GTPase activities significantly above basal levels in agonist-stimulated GTPase activity assays in cerebellar membranes. Furthermore, when using the method of agonist-stimulated [35S]GTPγS binding as assessed by autoradiography, we did not observe significant stimulation of [35S]GTPγS binding in rat brain sections by either (+)pentazocine or BD737. The above results demonstrate that the σ1 receptor is not likely be directly coupled to G proteins. (C) 2000 Elsevier Science B.V.

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