[Adverse Drug Reactions in Geriatric Psychiatric Patients - Influence of Potentially Inappropriate Drugs].

Objective: The purpose of this study was to examine the extent to which "potentially inappropriate drugs" (PID) are associated with an increased risk for adverse drug reactions (ADR).

Methods: Data from 304 geriatric psychiatric inpatients was collected. Medical documentation was used to find indications of ADRs.

[Hyperkinetic disorders in childhood and adolescence- an analysis of KinderAGATE 2009-2012].

Objective: This contribution evaluates the prevalence, medication use as well as age and sex distribution in inpatients with hyperkinetic disorders at the KinderAGATE hospitals for 2009-2012.

Method: The age, sex, leading diagnosis, prescribed medication, and dosage of each patient were recorded anonymously twice a year. They provide an outstanding epidemiological basis for the observation of the actual situation in child and adolescent psychiatry.

[Depressive disorders in childhood and adolescence - an analysis of KinderAGATE 2010].

Objective: The present analysis evaluates the prevalence and medication use in inpatients with depression during childhood and adolescence at the KinderAGATE hospitals in 2010. Also discussed are age and sex distribution.

Method: Since 2009 the following information has been recorded anonymously twice a year from each patient at the participating hospitals of KinderAGATE: age, sex, leading diagnosis, prescribed medication and dosage.

QTc prolongation by psychotropic drugs and the risk of Torsade de Pointes.

Introduction: Many psychotropic drugs can delay cardiac repolarization and thereby prolong the rate-corrected QT interval (QTc). A prolonged QTc often arouses concern in clinical practice, as it can be followed, in rare cases, by the life-threatening polymorphic ventricular tachyarrhythmia called torsade de pointes (TdP).

Method: We searched PubMed for pertinent literature on the risk of QTc prolongation and/or TdP associated with commonly used psychotropic drugs.

Properties of Arg389-beta1-adrenoceptor-Gsalpha fusion proteins: comparison with Gly389-beta1-adrenoceptor-Gsalpha fusion proteins.

The human beta1-adrenoceptor (beta1AR) exists in several isoforms and activates adenylyl cyclase (AC) via Gs-proteins. The Arg389-isoform of the beta1AR (beta1AR-R389) expressed in CHW cells is much more efficient than the Gly389 isoform of the beta1AR (beta1AR-G389) at stabilizing the ternary complex and activating AC (Mason et al. 1999).

The human formyl peptide receptor as model system for constitutively active G-protein-coupled receptors.

According to the two-state model of G-protein-coupled receptor (GPCR) activation, GPCRs isomerize from an inactive (R) state to an active (R*) state. In the R* state, GPCRs activate G-proteins. Agonist-independent R/R* isomerization is referred to as constitutive activity and results in an increase in basal G-protein activity, i.

Functional differences between human formyl peptide receptor isoforms 26, 98, and G6.

The formyl peptide receptor (FPR) is expressed in neutrophils, couples to G(i)-proteins and activates phospholipase C, chemotaxis and cytotoxic cell functions. FPR isoforms 26, 98, and G6 differ from each other in amino acids 101, 192 and 346 (FPR-26: V101, N192, E346; FPR-98: L101, N192, A346; FPR-G6: V101, K192, A346), but the functional significance of those structural differences is unknown. In order to address this question, we analyzed FPR-26, FPR-98 and FPR-G6 by co-expressing recombinant FLAG epitope-tagged FPRs with the G-protein G(i)alpha(2)beta(1)gamma(2) in Sf9 insect cells and measured high-affinity agonist binding and guanosine 5'- O-(3-thiotriphosphate) (GTPgammaS) binding.

Multiple differences in agonist and antagonist pharmacology between human and guinea pig histamine H1-receptor.

Species isoforms of histamine H2-, H3-, and H4-receptors differ in their pharmacological properties. The study aim was to dissect differences between the human H1R (hH1R) and guinea pig H1R (ghH1R). We coexpressed hH1R and gpH1R with regulators of G-protein signaling in Sf9 insect cells and analyzed the GTPase activity of Gq-proteins.

Critical role of N-terminal N-glycosylation for proper folding of the human formyl peptide receptor.

The human formyl peptide receptor (FPR) is N-glycosylated and activates phagocytes via G(i)-proteins. The FPR expressed with G(i)alpha(2)beta(1)gamma(2) in Sf9 insect cells exhibits high constitutive activity as assessed by strong inhibitory effects of an inverse agonist and Na(+) on basal guanosine 5(')-O-(3-thiotriphosphate) (GTPgammaS) binding. The aim of our study was to analyze the role of N-glycosylation in FPR function.

GDP affinity and order state of the catalytic site are critical for function of xanthine nucleotide-selective Galphas proteins.

Xanthine nucleotide-selective small GTP-binding proteins with an Asp/Asn mutation are valuable for the analysis of individual GTP-binding proteins in complex systems. Similar applications can be devised for heterotrimeric G-proteins. However, Asp/Asn mutants of Galpha(o), Galpha(11), and Galpha(16) were inactive.

Efficient adenylyl cyclase activation by a beta2-adrenoceptor-G(i)alpha2 fusion protein.

The G-protein G(i)alpha can activate adenylyl cyclase (AC), but the relevance of this AC activation is unknown. We used receptor-G protein co-expression and receptor-G protein fusion proteins to investigate G(i)alpha(2) regulation of AC in Sf9 cells. G(i)alpha(2) was fused to the beta(2)-adrenoceptor (beta(2)AR), a preferentially G(s)-coupled receptor, or the formyl peptide receptor (FPR), a G(i)-coupled receptor.

Constitutive activity of G-protein-coupled receptors: cause of disease and common property of wild-type receptors.

The aim of this review is to provide a systematic overview on constitutively active G-protein-coupled receptors (GPCRs), a rapidly evolving area in signal transduction research. We will discuss mechanisms, pharmacological tools and methodological approaches to analyze constitutive activity. The two-state model defines constitutive activity as the ability of a GPCR to undergo agonist-independent isomerization from an inactive (R) state to an active (R*) state.

Similarities and differences in the coupling of human beta1- and beta2-adrenoceptors to Gs(alpha) splice variants.

The human beta1-adrenoceptor (beta1AR) and beta2-adrenoceptor (beta2AR) couple to Gs-proteins to activate adenylyl cyclase (AC). There are differences in desensitization between the beta2AR and the originally cloned Gly389-beta1AR, but with respect to ternary complex formation, constitutive activity, and AC activation the picture is unclear. To learn more about the similarities and differences between the beta1AR and beta2AR, we analyzed coupling of the Gly389-beta1AR to the G(s(alpha)) splice variants Gs(alpha)L and Gs(alpha)S using beta1AR-Gs(alpha) fusion proteins expressed in Sf9 cells and compared the data with previously published data on beta2AR-Gs(alpha) fusion proteins (Seifert et al.

The human histamine H2-receptor couples more efficiently to Sf9 insect cell Gs-proteins than to insect cell Gq-proteins: limitations of Sf9 cells for the analysis of receptor/Gq-protein coupling.

The human histamine H2-receptor (hH2R) couples to Gs-proteins to activate adenylyl cyclase and to Gq-proteins to activate phospholipase C, but phospholipase C activation has not consistently been observed. The aim of this study was to compare coupling of hH2R to insect and mammalian Gs- and Gq-proteins in Spodoptera frugiperda (Sf9) cells. Interaction of hH2R with mammalian G proteins was assessed with coexpressed proteins or receptor-Galpha fusion proteins that enhance coupling efficiency.