The interaction of the carbostyril derivatives 5-[2-[[1-(4-aminophenyl)-2-methyl-prop-2-yl]amino]-1-hydroxyethyl]- 8-hydroxycarbostyril (carbo-amine) and 5-[2-[[3-[4-(bromoacetamido)phenyl]-2-methylprop-2-yl]amino]-1- hydroxyethyl]-8-hydroxycarbostyril (carbo-Br) with the rat reticulocyte beta-adrenoreceptor system has been partially characterized. In the absence of a guanine nucleotide, the concentration of carbo-amine, carbo-Br and (-)isoprenaline that inhibited (-)-[125I]iodocyanopindolol ([125I]CYP) binding by 50% (IC50) was 5.9 +/- 0.2, 3.3 +/- 0.3 and 49 +/- 3 nM, respectively. In the presence of a guanine nucleotide, the IC50 values were carbo-amine, 21 +/- 0.6 nM; carbo-Br, 7.6 +/- 0.3 nM and (-)isoprenaline, 813 +/- 66 nM. Preincubation of membranes with either of the carbostyril congeners followed by washing reduced specific [125I]CYP binding capacity without changing the KD value for the remaining receptors. The beta-antagonist nadolol largely prevented the receptor reduction induced by the carbostyril compounds. Incubation of membranes for 18 h at 25 degrees C resulted in an 11% recovery of the carbo-amine-induced receptor loss and no recovery of the receptors lost by preincubation with carbo-Br. However, the carbo-amine induced receptor loss could be largely reversed (80%) by membrane heating at 45 degrees C whereas little reversal (less than 10%) was observed with the carbo-Br pretreated membranes. The concentration of carbo-amine, carbo-Br and (-)isoprenaline that stimulated half-maximal cAMP formation in reticulocyte membranes was 17.8 +/- 3.1, 8.2 +/- 2.1 and 241 +/- 17 nM, respectively, and all 3 agonists produced the same maximal response. Initial cAMP formation stimulated by the carbostyril derivatives and (-)isoprenaline was blocked by concurrent addition of propranolol after 7 min of incubation with either of the two carbostyril derivatives did not affect further cAMP production whereas with (-)isoprenaline further cAMP production was blocked.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

PubMedDate not supplied

Aging changes in uptake of polysaccharides by human diploid cells in culture.

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Adsorption↗

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Insertion/deletion polymorphism in the angiotensin-converting enzyme gene in myocardial infarction survivors.

INTRODUCTION: Insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene influenced the plasma concentration of the ACE, and is D allele have been repetitively suggested as a risk factor for myocardial infarction (MI). MATERIAL AND METHODS: Two hundert thirty six male myocardial infarction survivors under 65 years and with body mass index and total plasma cholesterol levels under 95% of the Czech population were included in the study. As control group, 302 male controls (1% randomly selected group from the Czech population) were genotyped. I/D polymorphism in the ACE gene was determined using polymerase chain reaction. RESULTS: The prevalence of the I/I, I/D and D/D genotypes was 0.218, 0.494 and 0.288, in the control group, and 0.178, 0.538 and 0.284, in the myocardial survivors, respectively. The male Czech population has the similar frequency of insertion and deletion alleles compared to other Caucasian populations. The frequencies of the alleles and genotypes of the ACE gene did not differ significantly between MI survivors and a control sample of the Czech population. CONCLUSION: It was shown that the I/D polymorphism in the gene for ACE is not a genetic risk factor for myocardial infarction in the Czech population.

Adult↗