PubMed Health⌕ Search

Biomedical subjects

Charlotte Harrison

Publications and source records attributed to Charlotte Harrison.

5 recordsLinked to original sources
PubMed2005

Current methods used to investigate G protein coupled receptor oligomerisation.

Classical models of G protein coupled receptor (GPCR) signalling assume that each receptor functions as a single unit. However, evidence is increasing that GPCRs may form functional assemblies of dimeric or oligomeric units. There are several methods that can be used to give evidence of GPCR oligomerisation that will be discussed in this review. These include co-immunoprecipitation and Western blotting, resonance energy transfer methods and transactivation / complementation of partially functional receptors. One definitive method currently does not exist and there are various advantages and disadvantages to each method depending upon the system considered. Although co-immunoprecipitation and Western blot studies require disruption of the cellular environment and require specific antibodies, they are a good starting point to show that receptor oligomerisation occurs in native systems. Resonance energy transfer techniques provide evidence that receptors are in close proximity, are measured in living cells and some formats may be used for imaging applications. Transactivation / complementation requires extensive modification of the GPCR, but provides evidence that the receptors are in physical contact. Despite great advances being made using these techniques, future challenges involve the development of other methodologies to determine the role of receptor complexes in the pharmacology and physiology of native systems.

Animals↗
PubMed2004

Substance misuse services in secure psychiatric units.

Substance misuse is prevalent amongst patients detained in secure psychiatric hospitals in England, and is associated with more negative outcomes. However, no data has been published on the availability of substance misuse treatment services in secure units. This questionnaire-based study examined staff impressions of the prevalence and impact of substance misuse problems in secure units, and the availability of treatment services. It found that substance misuse was perceived as a major problem with a substantial impact. However, service provision was poor: some units had no access to treatment services at all and, when services were available, they tended to focus on awareness-raising or relapse prevention rather than treatment of current substance misuse. Few units appeared to be able to refer their patients to the local NHS addictions service.

Attitude of Health Personnel↗
PubMed2003

Endogenous RGS protein action modulates mu-opioid signaling through Galphao. Effects on adenylyl cyclase, extracellular signal-regulated kinases, and intracellular calcium pathways.

RGS (regulators of G protein signaling) proteins are GTPase-activating proteins for the Galpha subunits of heterotrimeric G proteins and act to regulate signaling by rapidly cycling G protein. RGS proteins may integrate receptors and signaling pathways by physical or kinetic scaffolding mechanisms. To determine whether this results in enhancement and/or selectivity of agonist signaling, we have prepared C6 cells stably expressing the mu-opioid receptor and either pertussis toxin-insensitive or RGS- and pertussis toxin-insensitive Galpha(o). We have compared the activation of G protein, inhibition of adenylyl cyclase, stimulation of intracellular calcium release, and activation of the ERK1/2 MAPK pathway between cells expressing mutant Galpha(o) that is either RGS-insensitive or RGS-sensitive. The mu-receptor agonist [d-Ala(2),MePhe(4),Gly(5)-ol]enkephalin and partial agonist morphine were much more potent and/or had an increased maximal effect in inhibiting adenylyl cyclase and in activating MAPK in cells expressing RGS-insensitive Galpha(o). In contrast, mu-opioid agonist increases in intracellular calcium were less affected. The results are consistent with the hypothesis that the GTPase-activating protein activity of RGS proteins provides a control that limits agonist action through effector pathways and may contribute to selectivity of activation of intracellular signaling pathways.

Adenylyl Cyclases↗