The Regulator of G Protein Signaling Homologous Domain of G Protein-Coupled Receptor Kinase 2 Mediates Short-Term Desensitization of β3-Adrenergic Receptor
G protein coupled receptor (GPCR) kinases (GRKs) are key regulators of GPCR signaling. Canonical mechanism of GPCR desensitization involves receptor phosphorylation by GRKs followed by arrestin recruitment and uncoupling from heterotrimeric G protein. Although β3-adrenergic receptor (β3AR) lacks phosphorylation sites by GRKs, agonist treatment proved to induce β3AR desensitization in many cell types. Here we show that GRK2 mediates short-term desensitization of β3AR by a phosphorylation independent mechanism but mediated by its domain homologous to the regulator of G protein signaling (RGS). HEK293T cells overexpressing human β3AR presented a short-term desensitization of cAMP response stimulated by the β3AR agonist, BRL37344, and not by forskolin. We found that β3AR desensitization was higher in cells co-transfected with GRK2. Similarly, overexpression of the RGS homology domain but not kinase domain of GRK2 increased β3AR desensitization. Consistently, stimulation of β3AR increased interaction between GRK2 and Gαs subunit. Furthermore, in rat cardiomyocytes endogenously expressing β3AR, transfection with dominant negative mutant of RH domain of GRK2 (GRK2/D110A) increased cAMP response to BRL37344 and inhibited receptor desensitization. We expect our study to be a starting point for more sophisticated characterization of the consequences of GRK2 mediated desensitization of the β3AR in heart function and disease.
Authors: Rohanachandra YM, Amarabandu HGI, Rohanachandra LT Abstract Parenting with mental illness is associated with family conflicts, parenting difficulties, low parental confidence and increased mental health and behavioural problems in children. Family focused interventions improve child outcomes by about 40 %. However, such services are not available in Sri Lanka.A cross sectional descriptive study was carried out in the general adult psychiatry follow-up clinics in a Teaching Hospital in Colombo, Sri Lanka to assess the needs of parents with mental illness. A specifically designed interviewer administered que...
Authors: Charnsil C, Narkpongphun A, Chailangkarn K Abstract AIMS: This research examines the prevalence of post-traumatic stress disorder (PTSD) and its related factors in students whose school burned down, one month and six months after the incident. METHODS: A total of 56 students from grades one through six were invited to participate in this study with permission from their parents. Subjects were screened for PTSD by using UCLA PTSD Reaction Index (DSM-5 Version) during three periods: 1, 6, and 12 months after the incident. Children diagnosed with PTSD were interviewed by a child and adolescent psychiatris...
Consultations in Liver Disease
Vinod K. Rustgi
NORMAN GITLIN, MD, FRCP (LONDON), FRCPE (EDINBURGH), FAASLD, FACP, FACG
CLINICS IN LIVER DISEASE
Hippocrates (460-371 bc) first recognized the relationship between the neuropsychological and physiologic changes observed in liver disease (Figs. 1 and 2). At that time, Hippocrates noted that there was a poor clinical outcome associated with delirium that was preceded by jaundice.1
We present a brief overview of the potential prophylactic and treatment agents under investigation, some which could be initiated in the ED if proven effective.
[Daily Maverick] While the promise of repositioning 'old' drugs such as chloroquine and hydroxychloroquine is tantalising, it is critical that the hazards of using unapproved treatments are shared with the public to prevent needless fatalities and supply shortages that may further burden already strained healthcare systems.