Comparative gene frequencies between the canchim breed of Brazil beef cattle and their foundation breeds

Panepucci, L.; Vicente, Vera

doi:10.1016/0305-0491(91)90323-6

Cited by 2 publications

(1 citation statement)

References 20 publications

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“…In contrast, multiple alleles of albumin are reported for rabbits (Ferrand and Rocha, 1992), cattle (Panepucci and Vicente, 1991), and monkeys (Watkins et al, 1993). If albumin polymorphism affects the pharmacokinetics and pharmacological effects of a drug candidate, care should be taken in the selection of strains or individual experimental animals.…”

Section: Discussionmentioning

confidence: 99%

Marked Strain Differences in the Pharmacokinetics of an α₄β₁Integrin Antagonist, 4-[1-[3-Chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]-methoxybenzoic Acid (D01-4582), in Sprague-Dawley Rats Are Associated with Albumin Genetic Polymorphism

Ito¹,

Takahashi²,

Sudo³

et al. 2006

J Pharmacol Exp Ther

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Strain differences in pharmacokinetics of an ␣ 4 ␤ 1 integrin antagonist, 4-[1-[3-chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]methoxybenzoic acid (D01-4582), in Sprague-Dawley rat strains (SD rat and CD rat) and their mechanism were investigated. Total plasma clearances of D01-4582 were 31.5 and 5.23 ml/min/kg in SD and CD rats, respectively. From in vivo studies, hepatic uptake process was thought to be involved in the strain differences. Differences in the uptake of D01-4582 by isolated hepatocytes prepared from the both strains were not observed when hepatocytes were incubated with simple buffer, but marked differences were observed when hepatocytes were incubated with plasma. When the dissociation constants (K d ) for the plasma protein binding of D01-4582 were examined in six rat strains, each strain was classified into two groups: a high-K d group, which included SD rats, Brown Norway rats, and Wistar rats; and a low-K d group, which included CD rats, Lewis rats, and Eisai hyperbilirubinemic rats. Since all rat strains in the low-K d group showed higher area under the concentration-time curve for D01-4582 than rats in the high-K d group, it was considered that the strain differences in the pharmacokinetics of D01-4582 were due to differences in the binding affinity. Purified albumin also showed strain differences in K d . The cDNA sequence of the albumin was analyzed, and 11 substitutions were observed. V238L and T293I were found only in the high-K d group, suggesting that these amino acid changes reduced the binding affinity of albumin for D01-4582. In conclusion, the strain differences in D01-4582 pharmacokinetics were suggested to be caused by an alteration in K d , associated with albumin genetic polymorphism.In the process of drug discovery and development, the properties of drug candidates are assessed and screened for their pharmacological, toxicological, and pharmacokinetic aspects. One important issue in the pharmacokinetic evaluation is the prediction of interindividual variabilities in plasma concentrations in humans. For this purpose, the metabolic pathway, elimination route, and their relevant proteins are characterized, because metabolism and membrane transport, in most cases, govern the plasma concentration profiles of a drug. Once the relevant protein, e.g., CYP3A4 or OATP1B1, has been identified, information on the frequency of the variants with reduced activity helps us to estimate the risk of the occurrence of interindividual variabilities (Sadee, 1998;Pirmohamed and Park, 2001;Tribut et al., 2002;Evans and McLeod, 2003). Animal models, such as knockout mice and naturally occurring deficient animals, are useful for demonstrating the importance of the protein in vivo. If pharmacokinetics differ in model animals compared with that in normal animals, the protein of interest would play an important role in vivo. In other words, pharmacokinetic differences in model animals would imply the possibility that interindiArticle, publication date, and...

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Section: Discussionmentioning

confidence: 99%

Marked Strain Differences in the Pharmacokinetics of an α₄β₁Integrin Antagonist, 4-[1-[3-Chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]-methoxybenzoic Acid (D01-4582), in Sprague-Dawley Rats Are Associated with Albumin Genetic Polymorphism

Ito¹,

Takahashi²,

Sudo³

et al. 2006

J Pharmacol Exp Ther

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Expression of multiple insulin and insulin-like growth factor receptor genes in salmon gill cartilage

Chan

Plisetskaya²,

Urbinati³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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In mammals, one of the major actions of insulin-like growth factor I (IGF-I) is to increase skeletal growth by stimulating new cartilage formation. IGF-I stimulates chondrocytes in vitro to synthesize new cartilage matrix, measured by enhanced uptake of 35 S-sulfate, but the addition of insulin does not produce a similar effect except when added at high concentrations. However, recent studies have shown that, in teleosts, both insulin and IGF-I are potent activators of 35 S-sulfate uptake in gill cartilage. To further characterize the growth-promoting activities of these hormones in fish, we have used reverse transcriptase-linked PCR to analyze the expression of insulin receptor family genes in salmon gill cartilage. Partial cDNA sequences encoding the tyrosine kinase domains from six distinct members of the IR gene family were obtained, and sequence comparisons revealed that four of the cDNAs encoded amino acid sequences that were highly homologous to human IR whereas the encoded sequences from two of the cDNAs were more similar to the human type I IGF receptor (IGF-R). Furthermore, a comparative reverse transcriptase-linked PCR assay revealed that the four putative IR mRNAs expressed in toto in gill cartilage were 56% of that found in liver whereas the expressed amount of the two IGF-R mRNAs was 9-fold higher compared with liver. These results suggest that the chondrogenic actions of insulin and IGF-I in fish are mediated by the ligands binding to their cognate receptors. However, further studies will be required to characterize the binding properties and relative contribution of the individual IR and IGF-R genes.

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Comparative gene frequencies between the canchim breed of Brazil beef cattle and their foundation breeds

Cited by 2 publications

References 20 publications

Marked Strain Differences in the Pharmacokinetics of an α₄β₁Integrin Antagonist, 4-[1-[3-Chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]-methoxybenzoic Acid (D01-4582), in Sprague-Dawley Rats Are Associated with Albumin Genetic Polymorphism

Marked Strain Differences in the Pharmacokinetics of an α₄β₁Integrin Antagonist, 4-[1-[3-Chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]-methoxybenzoic Acid (D01-4582), in Sprague-Dawley Rats Are Associated with Albumin Genetic Polymorphism

Expression of multiple insulin and insulin-like growth factor receptor genes in salmon gill cartilage

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Comparative gene frequencies between the canchim breed of Brazil beef cattle and their foundation breeds

Cited by 2 publications

References 20 publications

Marked Strain Differences in the Pharmacokinetics of an α4β1Integrin Antagonist, 4-[1-[3-Chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]-methoxybenzoic Acid (D01-4582), in Sprague-Dawley Rats Are Associated with Albumin Genetic Polymorphism

Marked Strain Differences in the Pharmacokinetics of an α4β1Integrin Antagonist, 4-[1-[3-Chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]-methoxybenzoic Acid (D01-4582), in Sprague-Dawley Rats Are Associated with Albumin Genetic Polymorphism

Expression of multiple insulin and insulin-like growth factor receptor genes in salmon gill cartilage

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Marked Strain Differences in the Pharmacokinetics of an α₄β₁Integrin Antagonist, 4-[1-[3-Chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]-methoxybenzoic Acid (D01-4582), in Sprague-Dawley Rats Are Associated with Albumin Genetic Polymorphism

Marked Strain Differences in the Pharmacokinetics of an α₄β₁Integrin Antagonist, 4-[1-[3-Chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidine-2-yl]-methoxybenzoic Acid (D01-4582), in Sprague-Dawley Rats Are Associated with Albumin Genetic Polymorphism