| 1. |
- Groenen, M. A., et al.
(författare)
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Analyses of pig genomes provide insight into porcine demography and evolution
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 491:7424, s. 393-398
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Tidskriftsartikel (refereegranskat)abstract
- For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
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| 2. |
- Arslan, G, et al.
(författare)
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P2Y receptors contribute to ATP-induced increases in intracellular calcium in differentiated but not undifferentiated PC12 cells
- 2000
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Ingår i: Neuropharmacology. - 1873-7064 .- 0028-3908. ; 39:3, s. 482-496
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Tidskriftsartikel (refereegranskat)abstract
- ATP-induced Ca2+ transients were examined in individual PC12 cells of a well defined clone, before and after treatment with nerve growth factor (NGF) to induce a neurone-like phenotype. Using reverse transcriptase PCR these cells were found to express mRNA for several P2 receptors. In undifferentiated cells the ATP-induced Ca2+ response was entirely dependent on Ca2+ influx, could not be mimicked by UTP, alpha,beta-methylene ATP or dibenzoyl ATP or be blocked by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). ATP had no significant effect on levels of cyclic AMP or inositol 1,4,5-trisphosphate (InsP3). These results suggest that in undifferentiated PC12 cells ATP mainly acts on a P2X receptor, possibly the P2X4 subtype. After treatment with NGF for 7 days the ATP response was increased and partially sensitive to PPADS. A component of the ATP-induced Ca2+ increase was due to mobilisation of intracellular Ca2+ stores and another to capacitative Ca2+ entry. UTP caused an increase in intracellular Ca2+, and InsP3 formation could be stimulated by ATP and UTP. ATP also caused a small increase in cyclic AMP, but this was abolished in the presence of indomethacin. Thus, after NGF treatment ATP acts partially via a P2Y receptor, possibly the P2Y2 subtype.
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| 3. |
- Klotz, K N, et al.
(författare)
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Comparative pharmacology of human adenosine receptor subtypes - characterization of stably transfected receptors in CHO cells
- 1998
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Ingår i: Naunyn-Schmiedeberg's Archives of Pharmacology. - 0028-1298. ; 357:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Four adenosine receptor subtypes of the family of G protein-coupled receptors, designated A1, A2A, A2B and A3 are currently known. In this study all human subtypes were stably transfected into Chinese hamster ovary (CHO) cells in order to be able to study their pharmacological profile in an identical cellular background utilizing radioligand binding studies (A1, A2A, A3) or adenylyl cyclase activity assays (A2B). The A1 subtype showed the typical pharmacological profile with 2-chloro-N6-cyclopentyladenosine (CCPA) as the agonist with the highest affinity and a marked stereoselectivity for the N6-phenylisopropyladenosine (PIA) diastereomers. In competition with antagonist radioligand biphasic curves were observed for agonists. In the presence of GTP all receptors were converted to a single low affinity state indicating functional coupling to endogenous G proteins. For A2A adenosine receptors CGS 21680 (2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadeno sine) and N-ethylcarboxamidoadenosine (NECA) were found to be the most potent agonists followed by R- and S-PIA with minor stereoselectivity. The relative potencies of agonists for the A2B adenosine receptor could only be tested by measurement of receptor-stimulated adenylyl cyclase activity. NECA was the most potent agonist with an EC50-value of 2.3 microM whereas all other compounds tested were active at concentrations in the high micromolar range. Inhibition of NECA-stimulated adenylyl cyclase identified xanthine amino congener (XAC; 8-[4-[[[[(2-aminoethyl)amino]-carbonyl]methyl]oxy]phenyl]-1,3-dipropylxa nthine) as the most potent antagonist at this receptor subtype. The A3 receptor was characterized utilizing the nonselective agonist [3H]NECA. The N6-benzyl substituted derivatives of adenosine-5'-N-methyluronamide (MECA) turned out to be the most potent agonists. The notion of xanthine-insensitivity of the A3 receptor should be dropped at least for the human receptor as xanthines with submicromolar affinity were found. Overall, the pharmacological characteristics of the human receptors are similar to other species with some species-specific characteristics. In this study we present for the first time the comparative pharmacology of all known human adenosine receptor subtypes. The CHO cells with stably transfected adenosine receptors provide an identical cellular background for such a pharmacological characterization. These cells are valuable systems for further characterization of specific receptor subtypes and for the development of new ligands.
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| 4. |
- Kull, B, et al.
(författare)
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Differences in the order of potency for agonists but not antagonists at human and rat adenosine A2A receptors
- 1999
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Ingår i: Biochemical Pharmacology. - 0006-2952. ; 57:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- To examine possible species differences in pharmacology, rat adenosine A2A receptors were studied in PC12 (pheochromocytoma) cells, and human receptors in Chinese hamster ovary (CHO) cells transfected with the cloned human A2A receptor cDNA. Using [3H]-5-amino-7(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine ([3H]-SCH 58261) as radioligand, the estimated Bmax (maximal binding) was 538 and 2085 fmol/mg in CHO and PC12 cells, respectively. The Kd (dissociation constant) values for [3H]-SCH 58261 were 1.05 and 5.6 nM in the two cell types, respectively. The order of potency of antagonists and most agonists was the same in both cell types, but 2-phenylaminoadenosine and 2-chloroadenosine were relatively less potent in PC12 cells than in CHO cells. In the functional assay, using cyclic AMP accumulation, all agonists tested were more potent in CHO than in PC12 cells, but this could not be readily explained by differences in adenylyl cyclase or in the expression of G proteins. As in the case of binding, the relative agonist potencies were similar for most compounds, but 2-phenylaminoadenosine and 2-chloroadenosine were more potent at human A2A receptors in CHO cells than predicted from the data obtained on rat A2A receptors in PC12 cells. Antagonists were approximately equipotent in the two cells. These results show that, despite only small differences in amino acid sequences and no difference in antagonist pharmacology, the relative order of potency of receptor agonists can differ between species homologues of the adenosine A2A receptor.
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| 5. |
- Kull, B, et al.
(författare)
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Reciprocal interactions between adenosine A2A and dopamine D2 receptors in Chinese hamster ovary cells co-transfected with the two receptors
- 1999
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Ingår i: Biochemical Pharmacology. - 0006-2952. ; 58:6, s. 1035-1045
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Tidskriftsartikel (refereegranskat)abstract
- Human adenosine A2A and rat dopamine D2 receptors (A2A and D2 receptors) were co-transfected in Chinese hamster ovary (CHO) cells to study the interactions between two receptors that are co-localized in striatopallidal gamma-aminobutyric acid-(GABA)ergic neurons. Membranes from transfected cells showed a high density of D2 (3.6 pmol per mg protein) and A2A receptors (0.56 pmol per mg protein). The D2 receptors were functional: an agonist, quinpirole, could stimulate GTPgammaS binding and reduce stimulated adenylyl cyclase activity. The A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) decreased high-affinity binding of the agonist dopamine at D2 receptors. Activation of adenosine A2A receptors shifted the dose-response curve for quinpirole on adenosine 3',5'-cyclic monophosphate (cAMP) to the right. However, CGS 21680 did not affect dopamine D2 receptor-induced GTPgammaS binding, but did cause a concentration-dependent increase in cAMP accumulation. The maximal cAMP response was decreased by the D2 agonist quinpirole in a concentration-dependent manner, but there was no change in EC50 and no effect in cells transfected only with adenosine A2A receptors. A2A receptor activation also increased phosphorylation of cAMP response element-binding protein and expression of c-fos mRNA. These effects were also strongly counteracted by quinpirole. These results show that the antagonistic actions between adenosine A2A and dopamine D2 receptors noted previously in vivo can also be observed in CHO cells where the two receptors are co-transfected. Thus, no brain cell-specific factors are required for such interactions. Furthermore, the interaction at the second messenger level and beyond may be quantitatively more important than A2A receptor-mediated inhibition of high affinity D2 agonist binding to the receptor.
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| 6. |
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| 7. |
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| 8. |
- Perez, M T, et al.
(författare)
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Release of endogenous and radioactive purines from the rabbit retina
- 1986
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 398:1, s. 12-106
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Tidskriftsartikel (refereegranskat)abstract
- The adenine nucleotide pool of rabbit retina was labeled by an intravitreal injection in vivo of [3H]adenosine. Practically all the radioactivity was retained in the form of adenine nucleotides. The relative proportion of [3H]adenine nucleotides was the same as that of endogenous nucleotides. Potassium depolarization (43.6 mM) in vitro caused a rapid increase in the rate of release of radioactive purines. The radioactive material was composed of hypoxanthine, xanthine, inosine and trace amounts of adenine, adenosine and adenine nucleotides. The release of radioactive purines was delayed and reduced by the addition of the nucleoside inhibitor dipyridamole suggesting that the purines may be released in the form of nucleosides. Similarly, the addition of the ecto 5'-nucleotidase inhibitor alpha, beta-methylene ADP (AOPCP) did not alter the release of radioactivity or the composition of the released purines. Endogenous hypoxanthine, xanthine and inosine could be detected in the effluents, but there was only a very modest increase following potassium depolarization. There was a slight, but significant, decrease in the release of endogenous adenosine and increase in AMP after AOPCP. It is concluded that there is an intensive uptake and phosphorylation of adenosine in the rabbit retina. Depolarization induces release of radioactive purine nucleosides and bases. Most of these compounds appear to be released as such, but in addition there may be a small (maximally a few per cent of the total) fraction of the purines that are released as nucleotides.
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| 9. |
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| 10. |
- Fredholm, B. B., et al.
(författare)
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Fuels for transportation
- 2010
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 39:suppl. 1, s. 31-35
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Tidskriftsartikel (refereegranskat)abstract
- There is a need to reduce the amount of fossil energy used for transport, both because of the easily available fossil fuel is becoming sparser and because of climate concerns. In this article, the concept of "peak oil" is briefly presented. Second, a practical approach to reduction of fossil fuel use for transport elaborated by two British commissions is presented. A key feature is the introduction of electric cars. This raises the third issue covered in this article: namely, how battery technology is going to meet the increasing needs posed by the transport sector
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