By using a strategy based on nucleotide sequence homology, we have cloned an intronless DNA encoding a new putative member of G protein-coupled receptors. The deduced amino acid sequence of the rat OL1 receptor, together with its expression at high levels in a small subset of cells in the olfactory neuroepithelium indicate that OL1 is related to the recently discovered olfactory multigene family. PCR and in situ hybridization analyses showed the OL1 transcripts to be not only expressed in the olfactory epithelium, but also in the heart. This unexpected cardiac expression was developmentally regulated, being maximal at early postnatal stages and hardly detectable at adult stages. Moreover, this observation was not restricted to OL1 since it was extended to other putative olfactory receptors. Although its functional significance remains unknown, this transient cardiac expression suggests that receptors belonging to the olfactory superfamily, could be not only involved in odor coding, but also in cardiac morphogenesis. Another olfactory-specific gene transcript encoding PTP NE-3, a recently cloned receptor-type protein-tyrosine phosphatase, could also be detected in heart. The very low levels of expression observed in rat embryo and at early postnatal stages as compared to adult stages, suggest that protein-tyrosine phosphatases, as well as protein-tyrosine kinases, may play a role in the control of cardiac cell growth and morphogenetic processes.

Amino Acid Sequence↗

PubMed1995

The D3 receptor and its relevance in psychiatry.

A large fraction of neurotensin neurons in the ventromedial shell subdivision of nucleus accumbens express D3 receptors. Blockade of D2/D3 receptors by antipsychotic agents paradoxically decreases neurotensin gene expression in these neurons whereas it enhances it in other striatal areas expressing the D2 receptor. This suggests that D2 and D3 receptors mediate opposite actions of dopamine. In support of this view low doses of nafadotride, a novel D3 receptor-preferring antagonist, enhances locomotor activity in rodents, a behavioral response opposite to that of current neuroleptics. The action of D3 receptor-preferring agonists was characterized by the mitogenic response they elicit in transfected NG 108-15 cells. Finally, gene expression of the D3 receptor is in opposition to that of the D2 receptor, being decreased by denervation and unaffected by chronic blockade by neuroleptics.

Antipsychotic Agents↗

PubMed1994

Opposing roles for dopamine D2 and D3 receptors on neurotensin mRNA expression in nucleus accumbens.

Using in situ hybridization histochemistry in rat nucleus accumbens, we show that the dopamine D3 receptor mRNA is expressed in the ventromedial part of the shell subdivision, where its gross distribution matches that of neurotensin mRNA. In addition, hybridization studies at the cellular level show that a large fraction of the neurotensin neurons co-express the D3 receptor mRNA in this restricted area. In contrast, the dopamine D2 receptor mRNA is expressed mainly in the core and marginally in the shell, at the level of the cone. In rats treated by haloperidol and sulpiride, two D2-like receptor antagonists, but not by SCH 23390, a D1-like receptor antagonist, proneurotensin mRNA was increased in the D2 receptor mRNA-rich areas but decreased in the D3 receptor mRNA-rich areas. This suggests that the D2 and D3 receptors control neurotensin mRNA expression negatively and positively, respectively.

Animals↗

PubMed1994

Disseminated cutaneous cryptococcosis. Comparison of clinical manifestations in the pre-AIDS and AIDS eras.

A review of the literature suggests some differences in the cutaneous manifestations of cryptococcosis present in patients in the pre-acquired immunodeficiency syndrome (AIDS) era compared with those manifestations that are present in today's AIDS era. In both periods, cutaneous manifestations can precede and be the sole clue to disseminated cryptococcal infection. Today, cutaneous cryptococcal involvement is often mistaken for molluscum contagiosum or Kaposi's sarcoma. We describe a patient with disseminated cryptococcosis who presented with skin lesions mimicking molluscum contagiosum, and who was subsequently shown to have AIDS.

AIDS-Related Opportunistic Infections↗

PubMed1994

Molecular cloning and characterization of the rat fifth melanocortin receptor.

Adrenocorticotropic hormone (ACTH) and melanocortin peptides (alpha, beta and gamma MSH) have numerous activities in both central nervous system and peripheral tissues, namely the adrenals. Recently, five melanocortin receptors were cloned and characterized. We report here the cloning, pharmacological characterization and expression of the rat fifth melanocortin receptor (MC5), starting from the dopamine D3 receptor sequence to screen a genomic DNA library. The MC5 comprises a sequence of 325 amino acids, displaying 45-62% identity with other melanocortin receptors and 82% identity with its human counterpart that we cloned thereafter. The sequence of the latter is identical to that of a so-called 'MC2' receptor (Chhajlani et al., 1993, Biochem. Biophys. Res. Comm. 195, 866-873). The MC5, stably expressed in CHO cells, mediates increase in cAMP accumulation with a characteristic pharmacology: alpha MSH is twice as potent as NDP alpha MSH, 10 times as ACTH and 100 times as gamma MSH. Very low expression levels were detected in brain, while high levels were found in adrenals, stomach, lung and spleen. In addition, in situ hybridization studies show the MC5 expressed in the three layers of the adrenal cortex, predominantly in the aldosterone-producing zona glomerulosa cells.

Adrenal Cortex↗

PubMed1994

Localization of the histamine H2 receptor and gene transcripts in rat stomach: back to parietal cells.

In contrast with many physiological studies suggesting that histamine H2 receptors are present on acid-secreting parietal cells of the gastric epithelium, it was recently shown that immune cells in the lamina propria are the only cells expressing H2-receptor mRNAs (Mezey and Palkovits, Science, 1992, 258, 1662-1665). We have reinvestigated the cellular localization of H2 receptors in the rat stomach by visualizing both the H2 receptor mRNA and the H2-receptor protein itself. In situ hybridization histochemistry performed with an antisense riboprobe for the rat H2 receptor, and autoradiographic distribution of 125I-aminopotentidine binding sites, a highly selective H2-receptor ligand, did not show any labeling of the lamina propria. Signals were clearly and solely detected in the gastric epithelium, the strongest being observed in the upper part of the glands where the H2 receptor gene transcripts were only detected within parietal cells. In situ hybridization performed with an antisense riboprobe for L-histidine decarboxylase mRNA confirmed the basal localization of the histamine-synthetizing cells in the rat gastric gland, at some distance from parietal histamine-sensitive cells.

Animals↗

PubMed1994

Evolutionary conservation of the AU-rich 3' untranslated region of messenger RNA.

AU-rich sequence motifs (specifically sequences containing reiterations of AUUUA) are found in the 3' untranslated region of mammalian mRNAs encoding cytokines, adhesion molecules, and protooncogenes. Because these AU-rich elements (3'AURE) have been observed to reduce the stability and translational efficiency of transcripts that contain them, and because many of these transcripts accumulate in cells exposed to inflammatory stimuli, we reasoned that mRNAs with 3'AURE may be highly conserved and that the AURE is a marker of mRNAs that are inducible by environmental stressors. To test this hypothesis, we developed a polymerase chain reaction (PCR) strategy to isolate specifically mRNAs with 3'AURE. We first validated the effectiveness of this approach by selectively amplifying two mRNAs containing 3'AURE from interleukin 1 (IL-1)-induced human endothelial cells, then used the same primers in reverse transcriptase-PCR of sea urchin RNA, and used the radiolabeled reaction products to screen a cDNA library prepared from endotoxin-exposed sea urchin coelomocytes. We identified 124 positive clones and isolated a 1608-base-pair fragment that contains an AU-rich consensus sequence upstream from a poly(A) tail. This sea urchin transcript hybridizes with immobilized poly(A)(+)-selected RNA prepared from living coelomocytes maintained in vitro for 8.5-13 h but not with RNA prepared from freshly harvested coelomocytes. Our results provide support for the growing body of evidence that 3' AURE are both conserved and functional and indicate further that isolation and short-term in vitro culture of sea urchin coelomocytes is sufficient to induce the expression of transcripts containing 3'AURE.

Animals↗

PubMed1994

Multiple dopamine receptors: the D3 receptor and actions of substances of abuse.

Our knowledge of dopamine receptor diversity has markedly increased during the past few years as a result of discovery of five distinct genes, splice variants and polymorphic receptors. The genes can be classified in two subfamilies: the intronless genes that encode the D1 and D5 receptors positively linked to adenylyl cyclase and genes with introns that encode the two isoforms of the D2 receptor and the D3 and D4 receptors. The various dopamine receptor subtypes can be distinguished by their sequence, intracellular signalling systems, pharmacology and localisation. The localisation of the D3 receptor in the shell of nucleus accumbens suggests its participation in brain reward circuits and actions of substances of abuse.

Animals↗

PubMed1994

Guinea pig histamine H1 receptor. I. Gene cloning, characterization, and tissue expression revealed by in situ hybridization.

An intronless DNA encoding the guinea pig H1 receptor was cloned from a genomic library using probes derived from the bovine H1 receptor. It encodes a protein of 488 amino acids with a calculated molecular mass of 55,619 daltons compared with a size of 56-68 kDa for the photoaffinity-labeled receptor as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The protein displays a 66% homology with the bovine receptor. Stable expression of the H1 receptor, characterized by the appearance of [3H]mepyramine binding sites with a pharmacology similar to that of the native H1 receptor, was obtained following transfection of Chinese hamster ovary cells. Southern blot analysis, using a variety of restriction enzymes, did not provide any evidence of multiple H1 isoreceptors. Northern blot analysis of a variety of guinea pig peripheral or cerebral tissues identified, in most cases, a single transcript of 3.3 kb, but also, in some tissues, a second transcript of 3.7 kb, possibly generated by the use of different promoter or polyadenylation sites or corresponding to a transcript from a distinct gene. In situ hybridization studies showed the highly contrasted cerebral expression of H1-receptor gene transcripts, which was compared with autoradiographic receptor localization. This allowed the identification of some major cell populations expressing the H1 receptor, e.g., Purkinje cells in cerebellum or pyramidal cells in the hippocampal complex.

Amino Acid Sequence↗

PubMed1994

Severe central nervous system toxicity after chronic treatment with cyclosporine.

Severe neurologic complications following treatment with cyclosporine are uncommon. They tend to occur during the first month of treatment and disappear after withdrawal or reduction of the dose of the drug. We report the case of a man who underwent a liver transplantation and subsequently developed severe central nervous system toxicity. After two years receiving cyclosporine, he presented with a brachial monoparesis and a complex visual disturbance. Symptoms slowly worsened during four months. On admission, he had confusion and seizures. Multiple areas of T2 prolongation, located in cerebral white matter, were seen on magnetic resonance imaging (MRI). Symptoms partially improved after cyclosporine withdrawal, but brain lesions shown on MRI persisted in serial imaging studies after two years of follow-up. We discuss the mechanisms that have been proposed to explain this clinical picture. Severe cyclosporine-associated neurotoxicity can also occur after chronic administration, even with serum levels in therapeutic range.

Brain Diseases↗

PubMed1994

The neuropeptide alpha-melanocyte-stimulating hormone inhibits experimental arthritis in rats.

alpha-Melanocyte-stimulating hormone (alpha-MSH) modulates inflammatory processes in models of acute inflammation and in models of sepsis/septic shock/adult respiratory-distress syndrome (ARDS). Because this neuropeptide inhibits actions of cytokines and other mediators of imflammation that are also believed to underlie aspects of chronic inflammation, tests were performed to compare the effects of repeated administration of the peptide with those of prednisolone and saline on the development of adjuvant arthritis in rats. alpha-MSH (50 micrograms), injected i.p. twice daily, markedly inhibited the clinical and histological signs of experimental arthritis and moderated the weight loss observed in control animals. Prednisolone (100 mg/kg), given twice per day, prevented development of arthritis but caused marked and progressive weight loss. The results confirm the potent anti-inflammatory influence of alpha-MSH, in this case in a model of chronic inflammation that has immune components.

Animals↗

PubMed1994

[Physicians denounce precariousness of reproductive health in the country and propose an addendum to the Brazilian document for the Cairo conference].

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Abortion, Induced↗