Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The biological activities of the proteinase-activated receptor number 2 (PAR-2)-derived peptides, SLIGRL (PP6) SLIGRL-NH2 (PP6-NH2) and SLIGR-NH2 (PP5-NH2) were measured in mouse and rat gastric longitudinal muscle (LM) tissue and in a rat aortic ring preparation and the actions of the PAR-2-derived peptides were compared with trypsin and with the actions of the thrombin receptor activating peptide, SFLLR-NH2 (TP5-NH2). 2. From a neonatal rat intestinal cDNA library, and from intestinal and kidney-derived cDNA, the coding region of the rat PAR-2 receptor was cloned and sequenced, thereby establishing its close sequence identity with the previously described mouse PAR-2 receptor; and this information, along with a reverse-transcriptase (RT) polymerase chain reaction (PCR) analysis of cDNA derived from gastric and aortic tissue was used to establish the concurrent presence of PAR-2 and thrombin receptor mRNA in both tissues. 3. In the mouse and rat gastric preparations, the PAR-2-derived polypeptides, PP6, PP6-HN2 and PP5-NH2 caused contractile responses that mimicked the contractile actions of low concentrations of trypsin (5 u/ml-1; 10 nM) and that were equivalent to contractions caused by TP5-NH2. 4. The cumulative exposure of the rat LM tissue to PP6-NH2 led to a desensitization of the contractile response to this polypeptide, but not to TP5-NH2 and vice versa, so as to indicate a lack of cross-desensitization between the receptors responsive to the PAR-2 and thrombin receptor-derived peptides. 5. In the rat gastric preparation, the potencies of the PAR-2-activating peptides were lower than the potency of TP5-NH2 (potency order: TP5-NH2 > > PP6-NH2 > or = PP6 > PP5-NH2); PP6 was a partial agonist in this preparation. 6. The contractile actions of PP6 and PP6-NH2 in the rat gastric preparation required the presence of extracellular calcium, were inhibited by nifedipine and were blocked by the cyclo-oxygenase inhibitor, indomethacin and by the tyrosine kinase inhibitor, genistein, but not by the kinase C inhibitor, GF109203X. The contractile responses were not blocked by atropine, chlorpheniramine, phenoxybenzamine, propranolol, ritanserin or tetrodotoxin. 7. In a precontracted rat aortic ring preparation, with an intact endothelium, all of the PAR-2-derived peptides caused a prompt relaxation response that was blocked by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME) but not by D-NAME; in an endothelium-free preparation, which possessed mRNA for both the PAR-2 and thrombin receptors, the PAR-2-activating peptides caused neither a relaxation nor a contraction, in contrast with the contractile action of TP5-NH2. The relaxation response to PP6-NH2 was not blocked by atropine, chlorpheniramine, genistein, indomethacin, propranolol or ritanserin. 8. In the rat aortic preparation, the potencies of PP6, PP6-NH2 and PP5-NH2 were greater than those of the thrombin receptor activating peptide, TP5-NH2 (potency order: PP6-NH2 > or = PP6 > PP5-NH2 > TP5-NH2). 9. In the rat aortic preparation, the relaxant actions of the PAR-2-derived peptides were mimicked by trypsin, at concentrations (0.5-1 u ml-1; 1-2 nM) lower than those that can activate the thrombin receptor. 10. The bioassay data obtained with the PAR-2 peptides and with trypsin, along with the molecular cloning/RT-PCR analysis, point to the presence of functional PAR-2 receptors that can activate distinct responses in the gastric and vascular smooth muscle preparations. These responses were comparable to those resulting from thrombin receptor activation in the same tissues, so as to suggest that the receptor for the PAR-2-activating peptides may play a physiological role as far reaching as the one proposed for the thrombin receptor.
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PMID:Rat proteinase-activated receptor-2 (PAR-2): cDNA sequence and activity of receptor-derived peptides in gastric and vascular tissue. 876 73

The endogenous, autosomal Tk gene is a potentially useful reporter of in vivo mutation since it may recover a wider range of mutational events than the X-linked Hprt gene or bacterial transgenes. In this study, we characterized mutations produced in the Tk gene of Tk(+/-) mice and compared them with mutations induced in the Hprt gene. Treatment of Tk(+/-) mice with N-ethyl-N-nitrosourea (ENU) resulted in dose-related increases in Tk mutants, as measured by the frequency of 5-bromodeoxyuridine-resistant (BrdUrd(r)) spleen lymphocytes. ENU-induced mutant frequencies in the Hprt gene, determined by measuring 6-thioguanine-resistant (TG(r)) lymphocytes, were similar to the Tk mutant frequencies. Allele-specific PCR of DNA from BrdUrd(r) lymphocyte clones suggested that 35% of clones from mice treated with ENU and 65% of clones from untreated animals had loss of heterozygosity (LOH) of the Tk gene due to deletion of the functional Tk allele. Reverse transcriptase-PCR/sequencing analysis of BrdUrd(r) and TG(r) clones from ENU-treated mice indicated that point mutations in both genes predominantly occurred at A:T basepairs; however, A:T-->G:C transition was the most common mutation in the Tk gene, while A:T-->T:A transversion was the most frequent mutation in the Hprt gene. Substitution at A:T basepairs in the Hprt gene occurred disproportionately with the mutated dT on the nontranscribed DNA strand, while this strand bias for mutation was not seen in the Tk gene. The results indicate that the specificity of ENU-induced point mutation differs between the two endogenous genes and that the autosomal Tk gene of Tk(+/-) mice is capable of recovering mutations caused by LOH. Environ. Mol. Mutagen. 34:30-38, 1999 Published 1999 Wiley-Liss, Inc.
Environ Mol Mutagen 1999
PMID:Molecular analysis of in vivo mutations induced by N-ethyl-N-nitrosourea in the autosomal Tk and the X-linked Hprt genes of mouse lymphocytes. 1046 21