PubMed Health⌕ Search

Biomedical subjects

G Coruzzi

Publications and source records attributed to G Coruzzi.

At least 145 records · Page 8Linked to original sources
PubMed1981

Assembly of the mitochondrial membrane system. Analysis of the nucleotide sequence and transcripts in the oxi1 region of yeast mitochondrial DNA.

The region of yeast mitochondrial DNA between 10.7 and 17.9 map units has been characterized by restriction analysis and DNA sequencing. The DNA sequence was obtained from the partially overlapping genomes of the two rho- mutants DS200/A1 and DS302. Two tRNA genes have been found in the sequence upstream of the oxi1 gene. The deduced secondary structures indicate that the genes code for the methionine (5'-CAU-3') and the asparagine (5'-GUU-3') tRNAs of yeast mitochondria. The region between 10.7 and 17.9 units contains two reading frames. One of these corresponds to the oxi1 gene previously shown to code for subunit 2 of cytochrome oxidase (Coruzzi, G., and Tzagoloff, A. (1979) J. Biol. Chem. 254,. 9324-9330; Fox, T. D. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 6534-6538). The second reading frame can potentially code for a basic protein with 386 amino acid residues. It is not known at present if this putative gene is translated in vivo. Northern blots of wild type mitochondrial RNA were hybridized to single-stranded probes from the oxi1 gene and flanking regions. The results of these analyses indicate that the primary transcript of the oxi1 region is a high molecular weight RNA (larger than 3 kilobase pairs) which is processed in discrete steps to a mature 850-nucleotide messenger. The 5' leader of the messenger has been established to be 54 nucleotides long and to have a sequence identical with that of the genomic DNA immediately upstream of the oxi1 gene.

Amino Acid Sequence↗
PubMed1981

Effect of some new Histamine H2-receptor antagonists on the guinea-pig papillary muscle.

Several histamine H2-receptor antagonists (cimetidine, ranitidine, oxmetadine and tiotidine) were tested for their activity on the papillary muscle of the guinea pig stimulated by histamine. All of the compounds exerted a competitive antagonism against histamine the order of potency being tiotidine greater than oxmetidine greater than ranitidine greater than cimetidine. Oxmetidine was the only drug which at high concentrations (10-6 M) decreased in maximum response of histamine probably because of non specific effects of the molecule already described in the literature. As it was expected, the H1-receptor antagonist, mepyramine, exerted a non-competitive antagonism.

Animals↗
PubMed1981

Effect of impromidine (SK&F 92676) on the isolated papillary muscle of the guinea-pig.

Impromidine was found to have a positive inotropic effect on the isolated papillary muscle from the guinea-pig. The dose-response curve to impromidine was shifted to the right by cimetidine and ranitidine. Impromidine was 35 times more potent than histamine but with a maximal response of only 81% that obtained with histamine. This difference, which was statistically significant (P < 0.005), suggested that impromidine acts as a partial agonist at the histamine H2-receptors of the papillary muscle as has been observed in other tissues.

Animals↗
PubMed1981

Effects of alkyl analogues of histamine and metiamide on the isolated guinea pig heart.

The effects of some substitutions in position 5(4) of the imidazole ring in the histamine and metiamide molecule were studied by means of isolated heart preparations from the guinea pig (atria and papillary muscle). Among the histamine analogues 5-methyl and 5-ethyl histamine were found to possess approximately the same intrinsic activity as histamine whereas 5-isopropylhistamine was shown to be absolutely inactive. Among the metiamide analogues the 5-ethyl derivative (etiamide) was found less effective than the parent substance but showed the same kind of competitive antagonism; the isopropyl derivative (isopropiamide) was found to be inactive up to a concentration of 3 X 10(-5) mol/l and to exert a non-competitive antagonism with 3 X 10(-4) mol/l. On the whole the atria and the papillary muscle preparations behaved quite similarly in regard to both the agonistic and the antagonistic compounds.

Animals↗
PubMed1981

Evidence for and against heterogeneity in the histamine H2-receptor population.

Evidence for and against heterogeneity in the histamine H2-receptor population is reported: it was based on different degrees of potency and also of efficacy among the H2-receptor-selective agonists; less striking but still evident differences in the potency of H2-antagonists; atypical interactions between H2-agonists and antagonists in particular experimental conditions and finally inability of H1- and H2-receptor antagonists to block some of the effects of histamine. Binding studies gave equivocal results. All the data reported in this review suggest that, although it is premature to speak about H2-receptor subtypes, further investigations are needed to check whether or not H2- and perhaps also H1-receptors represent homogeneous populations of histamine receptors.

Animals↗
PubMed1981

Effect of histamine and related compounds on gastric emptying of the conscious rat.

In conscious rats, histamine given intraperitoneally produced a delay in gastric emptying. A dose-dependent relationship was observed. The threshold dose was about 1 mg/kg, the calculated maximum dose 35 mg/kg. The inhibitory effect of histamine on gastric emptying was abolished by pretreatment with H1-receptor antagonists and mimicked by 2-aminoethylthiazole; on the contrary, an H2-receptor agonist (dimaprit) and H2 antagonists were completely ineffective. This suggested that receptors involved in delay of gastric emptying are of the H1 type. The inhibitory effect of histamine on gastric emptying was not modified by pretreatment with the well-known inhibitors of gastric secretion, metiamide and cimetidine. This is consistent with the idea that the delay in gastric emptying observed with histamine may not be related to the gastric properties of this compound.

Animals↗
PubMed1981

[Effect of H2 histamine receptor blocking agents on the isolated lower esophageal sphincter (LES) of the rat].

A series of histamine H2-receptor antagonists were tested for their activity on the isolated lower esophageal sphincter (LES) of the rat. Burimamide, methiamide and cimetidine were found to be virtually inactive since they caused very weak contractions only with extremely high concentrations (up to 300 microgram/ml). Ranitidine exerted a contraction at each concentration tested (from 1 to 100 microgram/ml). Oxmetidine, the newest member of the family, caused a modest contraction in low concentrations (0.3 to 3 microgram/ml) but a remarkable relaxation in high concentrations (10 to 300 microgram/ml). A series of observations suggested that H2 receptors do not occur in the rat LES: a) the lack of interference on histamine-induced contractions by the H2-blockers; b) the effect of histamine was mimiced by 2-aminoethylthiazole (a selective H1-receptor agonist) and inhibited by chlorpheniramine (a H1-receptor antagonist); c) dimaprit (a selective H2-receptor agonist) failed to modify the LES tension even at the maximum doses tested. All of these observations are consistent with the idea that the effects of the H2-receptor antagonists showed in the present investigation are independent of H2-receptor blockade. The contracting effect of ranitidine which was inhibited by tetrodotoxin and abolished by atropine is probably connected with a stimulating of the cholinergic system so far never described in the literature. The relaxant effect of oxmetidine is apparently a myolitic effect independent of stimulation of specific receptors.

Animals↗
PubMed1980

Assembly of the mitochondrial membrane system. Physical map of the Oxi3 locus of yeast mitochondrial DNA.

The oxi3 locus of yeast mitochondrial DNA is currently thought to code for Subunit 1 of cytochrome oxidase (Tzagoloff, A., Macino, G., and Sebald, W. (1979) Annu. Rev. Biochem. 48, 419-441). The respiratory competent strain of Saccharomyces cerevisiae D273-10B/A48 was used to obtain cytoplasmic "petite" clones enriched for genetic markers in the oci3 locus. The most complex clone studied (DS6) was ascertained to have a mitochondrial genome with a tandemly repeated segment of mtDNA 16.5 kilobases in length. The oxi3 locus was dissected by mutagenesis of DS6 with ethidium bromide and selection of new clones having less complex genotypes. Six derivative clones with genome sizes ranging from 2.3 to 6.1 kilobases have been extensively analyzed. Most of the restriction sites present in the segments of mtDNA retained by the clones have been mapped, thereby providing a detailed restriction map of the oxi3 gene. Based on the physical locations of the most distal oxi3 mutations, the gene spans approximately 10,000 nucleotides and occupies the region of wild type mtDNA from 44 to 58 map units.

DNA Restriction Enzymes↗
PubMed1980

Assembly of the mitochondrial membrane system. Structure and nucleotide sequence of the gene coding for subunit 1 of yeast cytochrme oxidase.

the oxi3 locus of yeast mitochondrial DNA has been sequenced in Saccharomyces cerevisiae D273-10B. The sequence was obtained from the mitochondrial genomes of a series of cytoplasmic "petite" mutants selected for the retention of genetic markers in the oxi3 locus. The oxi3 locus has been ascertained to code for Subunit 1 of cytochrome oxidase. The Subunit 1 gene is 9,979 nucleotides long, consisting of seven to eight exons that account for only 16% of the gene sequence. The coding sequences have been identified on the basis of protein sequence homology with Subunit 1 of human cytochrome oxidase. The yeast Subunit 1 is 510 amino acid residues long and has a molecular weight of 56,000. In addition to the exon sequences, the Subunit I gene contains six to seven introns. The first four introns have long reading frames that are continuous with the exon coding sequences. These reading frames are potentially capable of coding for basic proteins with molecular weights ranging from 30,000 to 80,000. The first two introns of the gene have a sequence homology of 50%, while the reading frame of the fourth intron is 70% homologous with an intron of the apocytochrome b gene. At least five stable transcripts have been found by Northern blot hybridizations with single-stranded DNA probes containing either exon or intron sequences. A 1.9-kolobase transcript hybridizes only with probes from the exon regions of the gene. This RNA species has been tentatively identified as the fully processed messenger of Subunit 1. Other transcripts are detected with intron probes. Three transcripts with sizes of 2.5, 2.4, and 0.85 kilobases appear to be stable excision products from the first, second, and fifth introns.

Amino Acid Sequence↗
PubMed1980

Transfer RNA genes in the cap-oxil region of yeast mitochondrial DNA.

A cytoplasmic "petite" (rho-) clone of Saccharomyces cerevisiae has been isolated and found through DNA sequencing to contain the genes for cysteine, histidine, leucine, glutamine, lysine, arginine, and glycine tRNAs. This clone, designated DS502, has a tandemly repeated 3.5 kb segment of the wild type genome from 0.7 to 5.6 units. All the tRNA genes are transcribed from the same strand of DNA in the direction cap to oxil. The mitochondrial DNA segment of DS502 fills a sequence gap that existed between the histidine and lysine tRNAs. The new sequence data has made it possible to assign accurate map positions to all the tRNA genes in the cap-oxil span of the yeast mitochondrial genome. A detailed restriction map of the region from 0 to 17 map units along with the locations of 16 tRNA genes have been determined. The secondary structures of the leucine and glutamine tRNAs have been deduced from their gene sequences. The leucine tRNA exhibits 64% sequence homology to an E. coli leucine tRNA.

Base Sequence↗
PubMed1980

Codon recognition rules in yeast mitochondria.

The mitochondrial genome of Saccharomyces cerevisiae codes for 24 tRNAs. The nucleotide sequences of the tRNA genes suggest a unique set of rules that govern the decoding of the mitochondrial genetic code. The four codons of unmixed fmilies are recognized by single tRNAs that always have a U in the wobble position of the anticodon. The codons of the mixed families are read by two different tRNAs. Codons terminating in a C or U are recognized by tRNAs with a G and codons terminating in a G or A are recognized by tRNAs with a U in the corresponding positions of the anticodons. There are two exceptions to these rules. In the AUN family for isoleucine and methionine, the isoleucine tRNA has a G and the methionine tRNA has a C in the wobble position. The tRNA for the arginine CGN family also has an A in the wobble position of the anticodon. It is of interest that the CGN codons have not been found in the mitochondrial genes sequenced to date. The simplified decoding system of yeast mitochondria allows all the codons to be recognized by only 24 tRNAs.

Anticodon↗
PubMed1980

Assembly of the mitochondrial membrane system: nuclear suppression of a cytochrome b mutation in yeast mitochondrial DNA.

In a previous study, a mitochondrial mutant expressing a specific enzymatic deficiency in co-enzyme QH2-cytochrome c reductase was described (TZAGO-LOFF, FOURY and AKAI 1976). Analysis of the mitochondrially translated proteins revealed the absence in the mutant of the mitochondrial product corresponding to cytochrome b and the presence of a new low molecular weight product. The premature chain-termination mutant was used to obtain suppressor mutants with wild-type properties. One such revertant strain was analyzed genetically and biochemically. The revertant was determined to have a second mutation in a nuclear gene that is capable of partially suppressing the original mitochondrial cytochrome b mutation. Genetic data indicate that the nuclear mutation is recessive and is probably in a gene coding for a protein involved in the mitochondrial translation machinery.

Cytochromes↗
PubMed1979

Assembly of the mitochondrial membrane system. DNA sequence of subunit 2 of yeast cytochrome oxidase.

A cytoplasmic "petitie" mutant of Saccharomyces cerevisiae (DS200/A1) has been isolated and determined to contain mitochondrial genetic markers in the oxi 1 locus. This locus has previously been reported to code for the structural gene of subunit 2 of cytochrome oxidase (Cabral et al. (1978) J. Biol. Chem. 243, 297-304). The segment of mitochondrial DNA retained in DS200/A1 has a repeat length of approximately 4500 base pairs and based on DNA sequencing contains a 756-nucleotide-long sequence that has been identified as the structural gene of subunit 2 of cytochrome oxidase. The presumptive gene sequence generates an amino acid sequence consistent with the reported molecular weight and composition of subunit 2 of yeast cytochrome oxidase. The correctness of the deduced amino acid sequence is further supported by its extensive homology to the primary structure of bovine cytochrome oxidase. The DNA segment of DS200/A1 has been located on the wild type mitochondrial DNA by comparative restriction mapping. The orientation of the COOH and NH2 termini and the direction of transcription of the gene have been determined.

Amino Acid Sequence↗