The biochemical abnormalities in transmembrane signal transduction mediated through G protein-coupled receptors (GPCRs) have been postulated as underlying pathophysiology of psychiatric diseases such as schizophrenia and mood disorders. In the present study, the experimental conditions of agonist-induced [35 S]GTPγS binding in postmortem human brain membranes were optimized, and the responses induced by a series of agonists were pharmacologically characterized. The [35 S]GTPγS binding assay was performed in postmortem human prefrontal cortical membranes by means of filtration techniques, and standardized as to GDP concentration, membrane protein content, MgCl2 and NaCl concentrations in assay buffer, incubation period, and effect of white matter contamination. Under the standard assay conditions, the specific [35 S]GTPγS binding was stimulated by the addition of 15 compounds in a concentration-dependent manner. Of these agonists, R(+)-8-OH-DPAT, UK-14,304, DAMGO, and DPDPE showed apparently biphasic concentration-response curves. As for these four responses, only higher-potency site was pharmacologically characterized. The receptors involved in the responses investigated were 5-HT1A receptor (probed with R(+)-8-OH-DPAT or 5-HT), α2A -adrenoceptor (UK-14,304 or (-)-epinephrine), M2 /M4 mAChRs (carbachol), adenosine A1 receptor (adenosine), histamine H3 receptor (histamine), group II mGlu (L-glutamate), GABAB receptor (baclofen), μ-opioid receptor (DAMGO or endomophin-1), δ-opioid receptor (DPDPE or SNC-80), and NOP (nociceptin). Although dopamine also activated specific [35 S]GTPγS binding, this response was likely mediated via α2A -adrenoceptor, but not dopamine receptor subtypes. The present study provides us with fundamental aspects of the strategy for elucidation of probable abnormalities of neural signalling mediated by G-proteins activated through multiple GPCRs in the brain of psychiatric patients. This article is protected by copyright. All rights reserved.

In the version of this paper originally published, the structure for epinephrine shown in Figure 1a was redrawn with an extra carbon. The structure has been replaced in the HTML and PDF versions of the article. The original and corrected versions of the structure are shown below.

Herein, we report an efficient electrochemical sensor strategy for determination of epinephrine based on Bi2O3 nanoparticle decorated reduced graphene oxide nanocomposite (Bi2O3@RGO). The Bi2O3@RGO was prepared by simple ultrasonic method and then it's morphological and crystal structure aspects were well characterized by physiological instruments. The electrode-electrolyte interfacial properties were examined to ensure the catalytic ability of composite sensing towards EP. The composite was deposited on the multi-conventional screen-printed electrode and was found to be desirable performance toward EP oxidation. The amperometric EP sensing exhibited good reproducible and sensitive which able to detect as low as concentration of 2.14 nM. Furthermore, good reproducibility, long-term stability and repeatability were obtained from the electrode in experiment. Moreover, the EP sensing method was successfully applied in human and rat blood serum, the recoveries were validated by HPLC method. It indicates the reliability of the method in practical analysis.

The catecholamines such as dopamine, norepinephrine, and epinephrine are neurotransmitters that regulate different physiological functions of the central nervous system. Some evidence suggest that the degeneration of dopamine neurons in the substantia nigra contributes in Parkinson's disease (PD), which is a neurodegenerative disorder and it is responsible for the major symptoms of PD. It is suggested that replenishment of striatal dopamine through the oral administration of the dopamine precursor, levodopa, can compensate the lack of endogenously produced dopamine. Some studies have shown the competitive inhibition of dopamine receptor such as methamphetamine, and other amphetamine-related derivatives, which block dopamine receptor activity to uptake dopamine.