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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent efforts in our laboratory have focused on cloning the molecular components involved in the cAMP-mediated pathway of olfactory signal transduction. These efforts have resulted in the isolation of olfactory-specific forms of a G protein, an adenylyl cyclase, and a cyclic nucleotide-gated cation channel. Functional expression of each of these proteins in vitro confirms their ability to carry out the function ascribed to them as part of a second-messenger cascade. Putative odorant-receptor molecules which constitute the first step in odorant signal transduction have now been cloned. We have generated oligonucleotide probes which recognize a population of olfactory receptors apparently more heterogeneous than those previously reported. These probes should enable us to answer questions regarding the number of different receptors expressed per cell as well as the nature of receptor-ligand specificity.
J Steroid Biochem Mol Biol 1991 Oct
PMID:Signal transduction in olfactory neurons. 165 79

Using multiple 35S-labeled oligonucleotide probes concurrently, the type I insulin-like growth factor receptor (IGF-I-R) mRNA was demonstrated by Northern blot hybridization in newborn and adult rat brain as a single species of approximately 11 kilobases. The probes were used to localize IGF-I-R mRNA by in situ hybridization in slices of adult rat brain. The highest levels of IGF-I-R mRNA expression were found in the glomerular and mitral cell body layers of the olfactory bulb, the granule cell body layers of the dentate gyrus and cerebellum, the pyramidal cell body layers of the piriform cortex and Ammon's horn, and the choroid plexus. The lowest levels of IGF-I-R mRNA expression were found in white matter. At the cellular level, IGF-I-R mRNA was expressed by a variety of neurons, by epithelial cells of the choroid plexus, and by ependymal cells of the third ventricle. Of the neuron types studied, the highest levels of IGF-I-R mRNA were consistently found in perikarya of mitral and tufted cells in the olfactory bulb, in pyramidal cells of the piriform cortex and Ammon's horn, and in granule cells of the dentate gyrus. There was a close congruency between the distribution of IGF-I binding and IGF-I-R mRNA at the regional level. Neuropil layers in the cerebral cortex, olfactory bulb, hippocampus, and cerebellum contained a high level of IGF-I binding, whereas the adjacent cell body layers contained a high level of the IGF-I-R mRNA. We conclude that in these regions, IGF-I-R mRNA is synthesized in neuronal cell bodies, and the receptors are transported to axons and dendrites in adjacent synapse-rich layers, where appropriate IGF effects are achieved.
Mol Endocrinol 1991 Aug
PMID:Localization of type I insulin-like growth factor receptor messenger RNA in the adult rat brain by in situ hybridization. 165 38

The localization of neurons containing mRNA of the alpha 1 subunit of the gamma-aminobutyric acid-A (GABAA) receptor was examined in the rat forebrain by in situ hybridization histochemistry using an oligonucleotide probe for the alpha 1 subunit. Moderately to strongly labeled neurons were numerous in the mitral cell layer of the olfactory bulb, the anterior olfactory nucleus, the diagonal band of Broca, the globus pallidus, the tenia tecta, the hippocampal formation, the thalamic and subthalamic nuclei, the zona incerta, and the amygdaloid complex. A few positive neurons were found in the caudate-putamen, the lateral and medial septal areas, the nucleus accumbens, the bed nucleus of the stria terminalis, the ventral pallidum, and the hypothalamus. The distribution of neurons containing alpha 1 subunit mRNA in the forebrain was very similar to that of neurons expressing beta 2 subunit mRNA, suggesting that these two subunits frequently coexist in the same neurons in the forebrain.
Brain Res Mol Brain Res 1991 Oct
PMID:Distribution of GABAA-receptor alpha 1 subunit gene expression in the rat forebrain. 166 21

Thyroid hormone is important for normal brain development. Cellular responses to thyroid hormone are mediated by multiple nuclear receptors, classified into alpha- and beta-subtypes. In the rat, expression of both the alpha and beta genes results in several translation products. By using cRNA probes common to alpha transcripts or specific for alpha-1 and beta-1, we have studied the distribution of these transcripts in rat brain at different stages of development from embryonic day 14 to adult age by using in situ hybridization histochemistry. On embryonic day 14, the alpha-1 mRNA is already widely expressed at a low level in the developing brain. The alpha-1 mRNA is developmentally regulated and showed a peak in expression during the first 3 postnatal weeks in the cerebral cortex, amygdala, hippocampus, and cerebellum. The probe common to the alpha transcripts detected a widespread distribution and high levels of these forms in the same regions throughout postnatal development. The level of beta-1 mRNA before birth was low or undetectable. The beta-1 transcript showed developmental regulation as well, with a high level at birth in the mitral cell layer of the olfactory bulb, accumbens nucleus, caudate, and hippocampal field CA1 and increasing levels in other regions later during development. Complementary expression of the alpha and beta forms was seen in the cerebral cortex and hippocampus. The differential temporal and spatial distribution as well as coexpression at comparable levels in certain brain regions suggest different roles for the c-erbA proteins during brain development and in the mature animal.
Mol Endocrinol 1991 Sep
PMID:Independent expression of the alpha and beta c-erbA genes in developing rat brain. 166 15

In homogenate of rat olfactory bulb, the opioid receptor agonists beta-endorphin, Leu-enkephalin, and dynorphin A stimulated adenylate cyclase activity in a concentration-dependent manner, with half-maximal effects displayed at 22, 63, and 176 nM, respectively. The maximal stimulation of the enzyme activity corresponded to about a 40% increase of basal activity for all three peptides. Naloxone antagonized the stimulation of beta-endorphin, Leu-enkephalin, and dynorphin A, with pA2 values of 8.0, 7.7, and 8.1, respectively. Kinetic analysis performed with Leu-enkephalin showed that the opioid peptide increased the Vmax of the enzyme, without changing the Km for the substrate Mg-ATP. Moreover, the opioid stimulation was associated with a significant increase of the affinity of the enzyme for Mg2+ activation and occurred in membranes incubated in a Ca2(+)-free medium. Addition of exogenous GTP at micromolar concentrations was absolutely necessary for the detection of the opioid effect. Treatment of olfactory bulbs with cholera toxin did not alter the stimulation of adenylate cyclase by Leu-enkephalin. However, the opioid stimulation disappeared in membranes obtained from bulbs injected with pertussis toxin. These results demonstrate the presence in the brain of a new functional class of opiate receptors coupled to stimulation of adenylate cyclase via a transduction mechanism that is Ca2+ independent and seems to involve a pertussis toxin-sensitive GTP-binding protein.
Mol Pharmacol 1991 Apr
PMID:Naturally occurring opioid receptor agonists stimulate adenylate cyclase activity in rat olfactory bulb. 167 23

Previous studies have shown changes in both somatostatin (SS)- and proenkephalin(PE)-derived peptides in the brains of amygdaloid-kindled rats, suggesting possible roles for the peptides in the kindling process. In this study, we have extended this analysis by looking at the time course of changes in SS and PE mRNAs at various times after kindling, in comparison with a single non-convulsive stimulation. Blot analysis of total RNA showed increases in SS mRNA in striatum, frontal cortex and hippocampus of animals receiving only a single stimulation as well as kindled animals--the increase occurred 1-3 days following stimulation and levels were back to basal by 1 week. PE mRNA did not change. In situ hybridization analysis, one day after the last kindling stimulation, showed significant elevations of SS mRNA in CA1, CA2 and dentate gyrus of hippocampus and of PE mRNA in olfactory cortex that were specific to kindling. However, both a single stimulation and kindling increased PE mRNA in olfactory tubercle and arcuate nucleus. In contrast, a single electrical stimulus increased PE mRNA in ventral striatum and SS mRNA in cingulate cortex and olfactory tubercle. These data support the idea that changes of SS mRNA in hippocampus and of PE mRNA in olfactory cortex may be related to kindling, and point out the importance of using animals which receive a single electrical stimulus, rather than sham-operated animals, as controls.
Brain Res Mol Brain Res 1991 Oct
PMID:Alterations in somatostatin and proenkephalin mRNA in response to a single amygdaloid stimulation versus kindling. 168 28

The influence of kainic acid (KA)-induced limbic seizure activity on the expression of mRNA for nerve growth factor (NGF) in adult rat brain was studied using in situ hybridization and S1 nuclease protection techniques with RNA probes complementary to murine and rat NGF mRNA. Within hippocampus, intracerebroventricular injection of 0.5 microgram KA caused a dramatic bilateral increase in hybridization of the 35S-labeled cRNA within stratum granulosum. This increase was first evident 1 h post-KA, appeared maximal at approximately 20-fold control levels at 2-3 h post-injection, and declined to control levels by 48 h post-injection. During the period of maximal hybridization, all but the deepest cells within stratum granulosum appeared to be autoradiographically labeled. Hybridization of the NGF cRNA probe was also increased within superficial layers of piriform and entorhinal cortex and, to much lesser extent, within scattered neurons of layers II and III of neocortex in KA-treated rats. In olfactory cortical areas, hybridization was maximally elevated 15.5-24.5 h after KA injection. In contrast to these effects, KA treatment did not consistently influence the density of hybridization, or number of neurons labeled, within the dentate gyrus hilus or the hippocampus proper (CA1-CA3). In agreement with the in situ hybridization results, S1 nuclease protection assay detected KA-induced increases in hybridization within pooled dentate gyrus/CA1 samples, but not hippocampal CA3 samples. These data support the conclusion that seizure activity stimulates a transient increase in NGF expression by select populations of forebrain neurons and indicates that experimental seizure paradigms might be further exploited for analyses of the mechanisms of NGF regulation and processing in the adult brain.
Brain Res Mol Brain Res 1991 Jan
PMID:Kainic acid-induced seizures stimulate increased expression of nerve growth factor mRNA in rat hippocampus. 170 74

Monoclonal antibodies against the inhibitory glycine receptor of rat spinal cord were used to identify corresponding receptor polypeptides in goldfish CNS. Both Western blot analysis and quantitative receptor immunoassays revealed crossreacting antigens in goldfish brain membranes. A polypeptide of 46 kDa molecular weight is immunologically related to the 48 kDa alpha subunit of the mammalian receptor. Similarly, a large receptor-associated protein of 93 kDa is present both in goldfish and mammals. Throughout the goldfish CNS, glycine-displaceable [3H]strychnine binding codistributes with the alpha subunit protein as determined immunologically. Glycine receptor contents were highest in goldfish medulla oblongata, medium in optic tectum and mesencephalon, whereas little or no receptor was detected in cerebellum, olfactory bulb, and spinal cord. Immunohistochemistry confirmed that the alpha subunit antigen and the 93 kDa protein were located in the plasma membrane of neurons and concentrated in small clusters found on the soma and dendrites. These data indicate that immunological properties and cellular distribution of glycine receptors are conserved from fish to mammals.
Brain Res Mol Brain Res 1991 Oct
PMID:Conservation of antigenic epitopes of the inhibitory glycine receptor in rodent and goldfish CNS. 172 95

The majority of astroglia develop postnatally in rats. GFAP (glial fibrillary acidic protein)-immunoreactivity appears mainly during the 2nd and 3rd postnatal weeks throughout the brain. Hypothyroidism inhibits, among others, the cell proliferation, maturation, and migration of neurons. However, hardly any data on the effect of hypothyroidism on GFAP-immunoreactivity are available in the literature. In our experiments, thyroidectomy was performed between the 3rd and 5th postnatal days. Operated and control animals from the same litter were perfused transcardially and processed for immunohistochemistry in parallel after 2, 3, and 4 wk. On the basis of serial sections, the development of GFAP-immunoreactivity was not generally affected by hypothyroidism. We could observe only two phenomena that showed a tendency of retardation in the operated animals: (1) the decrease of the strong GFAP-immunopositivity of white matter tracts (for example, internal capsule and pyramidal tract) and (2) the gradual disappearance of the GFAP-immunoreactive radial fibers (for example, in the neocortex, in the olfactory bulb, and around the 3rd ventricle).
Mol Chem Neuropathol 1991 Oct
PMID:Development of glial fibrillary acidic protein immunoreactivity in thyroidectomized rats. 177 89

Pregnenolone (P) and dehydroepiandrosterone (D) accumulate in the brain as unconjugated steroids and their sulfate (S) and fatty acid (L) esters. The microsomal acyl-transferase activity is highest in immature (1-3 weeks old) male rats. The immunocytochemical and biochemical evidence for P biosynthesis by differentiated oligodendrocytes is reviewed. The importance of P synthesis for its brain accumulation is assessed by the intracysternal injection of the inhibitor aminoglutethimide. Primary glial cell cultures convert P to 20-OH-P, PL, progesterone, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnane-20-one (Polone). Astroglial cell cultures also produce these metabolites, whereas neurons from 17-day mouse embryos only form 20-OH-P. P and D are converted to the corresponding 7 alpha-hydroxylated metabolites by a very active P-450 enzyme from rat brain microsomes. Several functions of neurosteroids are documented. P decreases in olfactory bulb of intact male rats exposed to the scent of estrous females. D inhibits the aggressive behavior of castrated male mice towards lactating female intruders. The D analog 3 beta-methyl-androst-5-en-17-one, which cannot be metabolized into sex steroids and is not demonstrably androgenic or estrogenic is at least as efficient as D. Both compounds elicit a marked decrease of PS in rat brain. The Cl- conductance of gamma-aminobutyric (GABAA) receptor is stimulated by GABA agonists, an effect which is enhanced by Polone and antagonized by PS. Thus, P metabolites in brain as well as steroids of extraencephalic sources may be involved physiologically in GABAA receptor function. The neurosteroids accumulated in brain may be precursors of sex steroid hormones and progesterone receptors have been localized in glial cells. P and D do not bind to any known intracellular receptor. A heat stable P binding protein has been found in brain cytosol with distinct ligand specificity. A binding component specific for steroids sulfates, including Polone S, DS and PS, in the order of decreasing affinity is localized in adult rat brain synaptosomal membranes. Its relationship to the GABAA receptor is under current investigation.
J Steroid Biochem Mol Biol 1991
PMID:Neurosteroids: biosynthesis, metabolism and function of pregnenolone and dehydroepiandrosterone in the brain. 183 45


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