The principal inhibitory neurotransmitter GABA (gamma-aminobutyric acid) exerts its effects through two ligand-gated channels, GABA(A) and GABA(C) receptors, and a third receptor, GABA(B) , which acts through G proteins to regulate potassium and calcium channels. Cells heterologously expressing the cloned DNA encoding the GABA(B)R1 protein exhibit high-affinity antagonist-binding sites, but they produce little of the functional activity expected from studies of endogenous GABA(B) receptors in the brain. Here we describe a new member of the GABA(B) polypeptide family, GABA(B)R2, that shows sequence homology to GABA(B)R1. Neither GABA(B)R1 nor GABA(B)R2, when expressed individually, activates GIRK-type potassium channels; however, the combination of GABA(B)R1 and GABA(B)R2 confers robust stimulation of channel activity. Both genes are co-expressed in individual neurons, and both proteins co-localize in transfected cells. Moreover, immunoprecipitation experiments indicate that the two polypeptides associate with each other, probably as heterodimers. Several G-protein-coupled receptors (GPCRs) exist as high-molecular-weight species, consistent with the formation of dimers by these receptors, but the relevance of these species for the functioning of GPCRs has not been established. We have now shown that co-expression of two GPCR structures, GABA(B)R1 and GABA(B)R2, belonging to the same subfamily is essential for signal transduction by GABA(B) receptors.

Two structurally related, G-protein-coupled receptors were identified as receptors for the neuropeptide, neuromedin U. This peptide is found in highest levels in the gut and genitourinary system where it potently contracts smooth muscle but is also expressed in the spinal cord and discrete regions of the brain. Binding sites for neuromedin U have been characterized in rat uterus, however, little is known about the activity of this peptide in the regions of the central nervous system where it is expressed. The receptors characterized in this report are activated by neuromedin U at nanomolar potency in heterologous expression systems and bind radiolabeled neuromedin U with high affinity. Localization of the receptor RNA by quantitative reverse transcription-polymerase chain reaction in a variety of human tissues shows distinct expression patterns for the two receptors. NMU1 is expressed predominantly in peripheral tissues, whereas NMU2 is more highly expressed in the central nervous system. Identification of neuromedin U receptor subtypes will greatly aid in the determination of the physiological roles of this peptide.

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Background Our objective was to retrospectively analyze the evolution of clinical features and thin-section computed tomography (CT) imaging of novel coronavirus disease 2019 (COVID-19) pneumonia in 17 discharged patients. Methods Serial thin-section CT scans of 17 discharged patients with COVID-19 were obtained during recovery. Longitudinal changes of clinical parameters and a CT pattern were documented in all patients during the 4 weeks after admission. A CT score was used to evaluate the extent of the disease. Results There were marked improvements of fever, lymphocyte counts, C-reactive proteins, and erythrocyte sedimentation rates within the first 2 weeks after admission. However, the mean CT score rapidly increased from the first to the third week, with a top score of 8.2 obtained in the second week. During the first week, the main CT pattern was ground-glass opacities (GGO; 76.5%). The frequency of GGO (52.9%) decreased in the second week. Consolidation and mixed patterns (47.0%) were noted in the second week. Thereafter, consolidations generally dissipated into GGO, and the frequency of GGO increased in the third week (76.5%) and fourth week (71.4%). Opacities were mainly located in the peripheral (76.5%) and subpleural (47.1%) zones of the lungs; they presented as focal (35.3%) or multifocal (29.4%) in the first week and became more diffuse in the second (47.1%) and third weeks (58.8%), then showed a reduced extent in fourth week (50%). Conclusions The progression course of the CT pattern was later than the progression of the clinical parameters within the first 2 weeks after admission; however, there were synchronized improvements in both the clinical and radiologic features in the fourth week.