| 31. |
- Erlinge, David, et al.
(författare)
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Mitogenic effects of ATP on vascular smooth muscle cells vs. other growth factors and sympathetic cotransmitters
- 1993
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Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - 1522-1539. ; 265:4, s. 1089-1097
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Tidskriftsartikel (refereegranskat)abstract
- The sympathetic nervous system has been shown to exert a trophic influence on vascular smooth muscle cells (VSMC). Therefore, we studied the growth-regulating effects of the sympathetic cotransmitters ATP, neuropeptide Y (NPY), and norepinephrine (NE). ATP in concentrations of 1-100 microM greatly increased the incorporation of [3H]thymidine in VSMC from rat aorta and vena cava. ATP also increased cell number and total protein content. The maximal effect on [3H]thymidine incorporation was greater than for epidermal growth factor (20 ng/ml) or insulin (1 microgram/ml) and approximately one-half that of 10% fetal calf serum. The potency series of other nucleotides and analogues of ATP was ATP > beta, gamma-methyleneATP (AMP-PCP) > ADP > adenosine > alpha, beta- methyleneATP (AMP-CPP) > 2-methylthioATP, indicating involvement of a P2 receptor, however, it does not meet proposed pharmacological criteria of either the P2x or P2y subclass. Several proposed P2 receptor antagonists were without effect. The effect of ATP could be mediated by a "nucleotide receptor," since UTP also stimulated [3H]thymidine incorporation. In our model, there was a strong correlation between the mitogenic effects of ATP, AMP-CPP, AMP-PCP, and UTP and their ability to stimulate influx of extracellular Ca2+ (Ca2+o). Moreover, the mitogenic effect of ATP was increased by high concentrations of Ca2+o. Taken together with data showing the lack of involvement of several other second-messenger systems, this indicates a critical role for Ca2+o in mediating the mitogenic effects of ATP. Amiloride, known to inhibit the action of several growth factors, also inhibited ATP-induced mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 32. |
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| 33. |
- Faghihi, MA, et al.
(författare)
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Genetics of neurological disorders
- 2004
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Ingår i: Expert review of molecular diagnostics. - : Informa UK Limited. - 1473-7159 .- 1744-8352. ; 4:3, s. 317-332
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Tidskriftsartikel (refereegranskat)
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Frith, Martin C., et al.
(författare)
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Pseudo-messenger RNA : Phantoms of the transcriptome
- 2006
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 2:4, s. 504-514
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Tidskriftsartikel (refereegranskat)abstract
- The mammalian transcriptome harbours shadowy entities that resist classification and analysis. In analogy with pseudogenes, we define pseudo-messenger RNA to be RNA molecules that resemble protein- coding mRNA, but cannot encode full-length proteins owing to disruptions of the reading frame. Using a rigorous computational pipeline, which rules out sequencing errors, we identify 10,679 pseudo - messenger RNAs ( approximately half of which are transposonassociated) among the 102,801 FANTOM3 mouse cDNAs: just over 10% of the FANTOM3 transcriptome. These comprise not only transcribed pseudogenes, but also disrupted splice variants of otherwise protein- coding genes. Some may encode truncated proteins, only a minority of which appear subject to nonsense- mediated decay. The presence of an excess of transcripts whose only disruptions are opal stop codons suggests that there are more selenoproteins than currently estimated. We also describe compensatory frameshifts, where a segment of the gene has changed frame but remains translatable. In summary, we survey a large class of non- standard but potentially functional transcripts that are likely to encode genetic information and effect biological processes in novel ways. Many of these transcripts do not correspond cleanly to any identifiable object in the genome, implying fundamental limits to the goal of annotating all functional elements at the genome sequence level.
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| 38. |
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| 39. |
- Grundemar, L, et al.
(författare)
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Biphasic blood pressure response to neuropeptide Y in anesthetized rats
- 1990
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 179:1-2, s. 83-87
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Tidskriftsartikel (refereegranskat)abstract
- The effects of neuropeptide Y (NPY) on systemic arterial blood pressure and heart rate were studied in anesthetized intact and pithed rats. I.v. doses of NPY (0.3-30 nmol/kg) raised the mean arterial blood pressure dose dependently. At doses of greater than or equal to 3.0 nmol/kg, the initial pressor response was followed by a dose-dependent fall in blood pressure in intact and pithed rats. The depressor response was accompanied 1-2 min after the NPY injection by a slight increase in heart rate in pithed rats but not in intact rats, and 10 min after the injection by a decrease in heart rate in intact rats. After repeated injections of NPY, the depressor effect vanished, whereas the integrated pressor response over time was markedly enhanced. After pretreatment with the histamine H1-receptor antagonist, mepyramine, or with the histamine liberator, compound 48/80, the pressor response to NPY remained but the depressor response disappeared. We suggest that the marked fall in blood pressure can be attributed to NPY-evoked histamine release from mast cells.
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| 40. |
- Grundemar, L, et al.
(författare)
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Characterization of vascular neuropeptide Y receptors
- 1992
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188. ; 105:1, s. 45-50
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Tidskriftsartikel (refereegranskat)abstract
- 1. In the present study we compared neuropeptide Y (NPY) and NPY-related analogues for their ability to activate or bind to vascular NPY receptors in four experimental set-ups. Previous results have suggested the existence of different receptor subtypes, Y1 receptors requiring full-length NPY (1-36) or [Pro34]-NPY, and Y2 receptors recognizing also N-terminally truncated forms of NPY but not [Pro34]-NPY. 2. NPY 1-36 and [Pro34]-NPY dose-dependently increased arterial pressure in the anaesthetized rat with a similar magnitude and potency. NPY 2-36 was much less potent than NPY 1-36. NPY 4-36 and NPY 11-36 were inactive even at a dose as high as 10 nmol kg-1. 3. NPY 1-36, [Pro34]-NPY, NPY 2-36 and NPY 5-36 concentration-dependently increased the coronary resistance in the Langendorff preparation of the rat. NPY 1-36 and [Pro34]-NPY were equipotent, while NPY 2-36 and NPY 5-36 were about 7 and 20 times less potent. At 0.3 microM, NPY 11-36, NPY 20-36 and NPY 22-36 induced a slight contraction while NPY 23-36 was inactive. 4. NPY 1-36, [Pro34]-NPY, NPY 2-36, NPY 4-36, NPY 5-36 and NPY 11-36 evoked concentration-dependent contractions in the isolated inferior caval vein of the rat and guinea-pig. [Pro34]-NPY was more potent than NPY 1-36. NPY 2-36 was equipotent with NPY 1-36, while NPY 4-36, NPY 5-36 and NPY 11-36 were approximately 30 times less potent.5. [Pro34]-NPY was equipotent with NPY 1-36 in displacing the '25I-labelled gut hormone peptide([1251]-PYY) from rat aortic smooth muscle cells, while NPY 2-36 and shorter forms of NPY were much less potent or inactive.6. In caval vein smooth muscle cells of the rat, the displacement pattern was more complex than in aortic smooth muscle cells, in that both [Pro34]-NPY and NPY 13-36 effectively displaced the radioligand,albeit none of them completely.7. In conclusion, the NPY-evoked pressor response in the whole rat and coronary vessels seems to be mediated by vascular Y1 receptors and the binding characteristics of the NPY-related peptides in the aortic smooth muscle cells correspond to a population of such receptors. In the caval vein, the profile of the bioactivity and the binding affinity of the NPY-related peptides suggest a mixed population of Y1/Y2 receptors.
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