Receptor

About: Receptor is a research topic. Over the lifetime, 159318 publications have been published within this topic receiving 8299881 citations.

Distribution and targeting of a mu-opioid receptor (MOR1) in brain and spinal cord

Abstract: Opioid receptors regulate neuronal activity by both pre- and postsynaptic mechanisms We recently reported that the cloned delta- opioid receptor (DOR1) is primarily targeted to axons, suggesting a presynaptic role In the present study we have studied the distribution and targeting of another opioid receptor, the mu-opioid receptor (MOR1), by raising anti-peptide antisera to the C-terminal peptide of MOR1 The specificity of the antisera was determined by analysis of transfected cells, Western blots, and immunoisolation studies Immunohistochemistry showed that MOR1 immunoreactivity was enriched in many brain areas including cerebral cortex, striatum, hippocampus, locus coeruleus, and the superficial laminae of the dorsal horn Moreover, MOR1-expressing neurons seem to target this receptor preferentially to their somatodendritic domain as determined by double- labeling experiments with MAP2 However, discrete populations of neurons target MOR1 to their axons, including some primary afferent neurons that express DOR1 In many regions enkephalin-containing axons were complementary to MOR1, suggesting by their proximity that enkephalins may be physiologically relevant ligands for this receptor Thus, these results provide a morphological basis for understanding pre- and postsynaptic functions mediated by MOR1

Genes and ligands for odorant, vomeronasal and taste receptors

Abstract: The chemical senses (smell and taste) have evolved complex repertoires of chemosensory receptors — G-protein coupled receptors with a seven-transmembrane domain structure. In the mouse, ∼1,000 odorant receptors are dedicated to the conventional sense of smell, ∼300 vomeronasal receptors mediate the detection of chemical stimuli (such as pheromones) by the vomeronasal organ, and ∼40 taste receptors are implicated in bitter, sweet and umami taste. Nearly all receptor genes have now been identified as the result of genome sequencing, but few receptor–ligand interactions have been characterized. Targeted expression of the green fluorescent protein in chemosensory cells is a promising approach to achieve this objective.

Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine.

Abstract: Reduced glucose utilization and energy metabolism occur early in the course of Alzheimer's disease (AD) and correlate with impaired cognition. Glucose utilization and energy metabolism are regulated by insulin and insulin-like growth factor I (IGF-I), and correspondingly, studies have shown that cognitive impairment may be improved by glucose or insulin administration. Recently, we demonstrated significantly reduced levels of insulin and IGF-I polypeptide genes and their corresponding receptors in advanced AD relative to aged control brains. The abnormalities in gene expression were accompanied by impaired survival signaling downstream through PI3 kinase-Akt. The present work characterizes the abnormalities in insulin and IGF gene expression and receptor binding in brains with different Braak stage severities of AD. Realtime quantitative RT-PCR analysis of frontal lobe tissue demonstrated that increasing AD Braak Stage was associated with progressively reduced levels of mRNA corresponding to insulin, IGF-I, and IGF-II polypeptides and their receptors, tau, which is regulated by insulin and IGF-I, and the Hu D neuronal RNA binding protein. In contrast, progressively increased levels of amyloid beta protein precursor (AbetaPP), glial fibrillary acidic protein, and the IBA1/AIF1 microglial mRNA transcripts were detected with increasing AD Braak Stage. Impairments in growth factor and growth factor receptor expression and function were associated with increasing AD Braak stage dependent reductions in insulin, IGF-I, and IGF-II receptor binding, ATP levels, and choline acetyltransferase (ChAT) expression. Further studies demonstrated that: 1) ChAT expression increases with insulin or IGF-I stimulation; 2) ChAT is expressed in insulin and IGF-I receptor-positive cortical neurons; and 3) ChAT co-localization in insulin or IGF-I receptor-positive neurons is reduced in AD. Together, these data provide further evidence that AD represents a neuro-endocrine disorder that resembles a unique form of diabetes mellitus (? Type 3) and progresses with severity of neurodegeneration.

Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs.

Abstract: Bone morphogenic proteins (BMPs) are universal regulators of animal development. We report the identification and cloning of the BMP type II receptor (BMPR-II), a missing component of this receptor system in vertebrates. BMPR-II is a transmembrane serine/threonine kinase that binds BMP-2 and BMP-7 in association with multiple type I receptors, including BMPR-IA/Brk1, BMPR-IB, and ActR-I, which is also an activin type I receptor. Cloning of BMPR-II resulted from a strong interaction of its cytoplasmic domain with diverse transforming growth factor beta family type I receptor cytoplasmic domains in a yeast two-hybrid system. In mammalian cells, however, the interaction of BMPR-II is restricted to BMP type I receptors and is ligand dependent. BMPR-II binds BMP-2 and -7 on its own, but binding is enhanced by coexpression of type I BMP receptors. BMP-2 and BMP-7 can induce a transcriptional response when added to cells coexpressing ActR-I and BMPR-II but not to cells expressing either receptor alone. The kinase activity of both receptors is essential for signaling. Thus, despite their ability to bind to type I and II receptors receptors separately, BMPs appear to require the cooperation of these two receptors for optimal binding and for signal transduction. The combinatorial nature of these receptors and their capacity to crosstalk with the activin receptor system may underlie the multifunctional nature of their ligands.