RESUMO
A huge number of natural and synthetic compounds modulate the function of the γ-aminobutyric acid type A receptor (GABAA-R) by interacting with several allosteric binding sites which may differ in the various GABAA-R subtypes. The benzodiazepine receptor (BDZ-R) is the most intensively studied allosteric site. It is the first allosteric modulatory site on a neurotransmitter receptor that has been found to mediate two opposite functions: facilitation and depression of GABAA-R function. The effects of BDZ-R ligands on behavior range from agonistic (anxiolytic, anticonvulsant, myore-laxant/ataxic and hypno-sedative effects) to inverse-agonistic (anxiety and panic, hypervigilance and convulsions). Of particular interest for the future are BDZ-R partial agonists, as they lack several of the undesired properties of classic full agonists. Furthermore the GABAA-R system shows a high plasticity. This polymorphism raises the possibility that ligands selective for distinct subtypes of BDZ-R may emerge as useful drugs. In both cases the possibility exists of achieving very subtle manipulations of GABAA-R function by using allosteric modulators.
RESUMO
In this first part of a review on recent insights into the structure and function of the γ-aminobuty rie acid type A - benzodiazepine receptor system, the γ-aminobutyric acid type A (GABAA) receptor and the different types of benzodiazepine (BDZ) receptors known at this moment are dicussed. GABAA- and BDZ receptors are coupled in a supramolecular GABAA-BDZ-ionophore receptor complex, each consisting of five acidic glycoprotein molecules called subunits. These subunits can be classified into five groups: α, ß, γ, σ and ρ. Present evidence indicates the existence of multiple subtypes of these subunits. Multiple GABAA-BDZ receptors exist in the brain that show differential distribution and developmental patterns. These receptors differ from their subunit composition. The final functional properties of the receptor are determined by the different subunits constituting this receptor. Heterogeneity among α- subunits may determine the diversity of BDZ pharmacology in different regions of the nervous system.
RESUMO
A study was undertaken to determine whether the 48 anaesthetists in Bloemfontein have a higher rate of exposure to hepatitis B virus than comparable groups and whether active immunisation with hepatitis B surface antigen is necessary. Hepatitis B markers were detected by radio-immunoassay and the results analysed statistically. Hepatitis B markers were found in the sera of 36.17% of the anaesthetists and they had an 8-9 times greater prevalence of markers than employees of the local hospitals. Hence anaesthetists run a larger risk of contracting hepatitis B and its complications. It is recommended that non-immune anaesthetists be immunised.