Arprinocid, an inhibitor of hypoxanthine- guanine transport

Wang, Ching C.; Tolman, Richard L.; Simashkevich, Paula M.; Stotish, Ronald L.

doi:10.1016/0006-2952(79)90686-5

Cited by 17 publications

(4 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This drug is metabolized in the chicken and excreted primarily as arprinocid-1-N-oxide ( Wang et al 1979a;Wang and Simashkevich 1980). The mode of action of either of these two compounds is unclear, although it has been suggested that their mechanism may involve cytochrome P-450-mediated microsomal metabolism leading to the destruction of the endoplasmic reticulum and to cell death (Wang et al 1979b;Wang et al 1981).…”

Section: Discussionmentioning

confidence: 99%

A Genetic Linkage Map of the Apicomplexan Protozoan Parasite Eimeria tenella

Shirley¹,

Harvey²

2000

Genome Res.

View full text Add to dashboard Cite

Apicomplexan protozoan parasites have complex life cycles that involve phases of asexual and sexual reproduction. Some genera have intermediate insect hosts, for example, Plasmodium spp. (the cause of malaria), but related genera such as Eimeria spp. (causative agents of coccidiosis in poultry) have a direct life cycle occurring in only a single host. Mechanisms that regulate the life cycles of apicomplexan parasites are unknown, but the intracellular growth of avian Eimeria spp. is easily shortened by serial selection for the first parasites to complete the transition from asexual to sexual reproduction (to yield so-called precocious lines). To investigate the genetic basis of such an abbreviated life cycle, we have used the species E. tenella and analyzed the inheritance of 443 polymorphic DNA markers in 22 recombinant cloned progeny derived from a cross between parents that had selectable phenotypes of precocious development or resistance to an anticoccidial drug. The markers were placed in 16 linkage groups (which defined 12 chromosomes) and a further 57 unlinked groups. Two linkage groups showed an association (P = .0105) with the traits of precocious development or drug-resistance and were mapped to chromosome 2 (ca 1.2 Mbp) and chromosome 1 (ca 1.0 Mbp), respectively. The map provides a framework for further studies on the identification of genetic loci implicated in the regulation of the life cycle of an important protozoan parasite and a representative of a major taxonomic group.[A table with the segregation data is available as an online supplement at http://www.genome.org.]

show abstract

Section: Discussionmentioning

confidence: 99%

A Genetic Linkage Map of the Apicomplexan Protozoan Parasite Eimeria tenella

Shirley¹,

Harvey²

2000

Genome Res.

View full text Add to dashboard Cite

show abstract

“…For confirmation it would be necessary to analyse the active metabolite produced in the medium during the growth of chick embryo liver cell cultures. Arprinocid is claimed to be an inhibitor of hypoxanthine-guanosine transport, as demonstrated by the inhibition of pulse-labelling of nucleic acids by hypoxanthine in cell culture (Wang, Simashkevich & Stotish, 1978). Wolf et al (1978) also stated that microsomal preparations from rat and mouse liver converted arprinocid to 2-chloro-6-fluorobenzyl alcohol and not to the iV-oxide.…”

Section: Discussionmentioning

confidence: 99%

Factors influencing the assessment of anticoccidial activity in cell culture

Latter

Wilson²

1979

Parasitology

View full text Add to dashboard Cite

SUMMARYA comparative study has been made of the factors influencing the assessment of anticoccidial potency in vitro against Eimeria tenella using established anticoccidials and arprinocid and some of its analogues. Drugs whose potency depended upon medium composition were amprolium, lasalocid and halofuginone. There was a difference in strain sensitivity with robenidine. Host cell type had an important effect on potency of monensin, decoquinate, arprinocid and its analogues. Arprinocid was active in chick liver cell systems but totally inactive in chick kidney cell systems, although its N-oxide was active in both cell types. Arprinocid-containing medium, conditioned by supporting the growth of chick embryo liver cell cultures, had an anticoccidial effect on E. tenella, growing in chick kidney cells. It is deduced that the anticoccidial activity of arprinocid in the chick is due to a metabolite.

show abstract

“…Briefly, the first parent used for the cross was the WisF125 precocious line (a faster life cycle ; Jeffers, b, 1975 and the second parent was a line derived from the W reference strain made resistant to the anticoccidial drug arprinocid. This drug is metabolised in the chicken and excreted primarily as arprinocid-1-N-oxide (Wang et al 1979 ;Wang & Simashkevich, 1980). The parasites recovered, referred to as the Progeny of the Cross, were passaged in the face of both selection pressures and recombinant parasites, defined by both drug-resistance and faster development, were recovered and used to establish 22 clonal populations each from infection with a single sporocyst.…”

Section: G E N O M E S a N D C H R O M O S O M E S O F E I M E R I A mentioning

confidence: 99%

Integrating genetics and genomics to identify new leads for the control ofEimeriaspp.

Shirley¹,

Blake²,

White³

et al. 2004

Parasitology

View full text Add to dashboard Cite

Eimerian parasites display a biologically interesting range of phenotypic variation. In addition to a wide spectrum of drug-resistance phenotypes that are expressed similarly by many other parasites, the Eimeria spp. present some unique phenotypes. For example, unique lines of Eimeria spp. include those selected for growth in the chorioallantoic membrane of the embryonating hens egg or for faster growth (precocious development) in the mature host. The many laboratory-derived egg-adapted or precocious lines also share a phenotype of a marked attenuation of virulence, the basis of which is different as a consequence of the in ovo or in vivo selection procedures used. Of current interest is the fact that some wild-type populations of Eimeria maxima are characterized by an ability to induce protective immunity that is strain-specific. The molecular basis of phenotypes that define Eimeria spp. is now increasingly amenable to investigation, both through technical improvements in genetic linkage studies and the availability of a comprehensive genome sequence for the caecal parasite E. tenella. The most exciting phenotype in the context of vaccination and the development of new vaccines is the trait of strain-specific immunity associated with E. maxima. Recent work in this laboratory has shown that infection of two inbred lines of White Leghorn chickens with the W strain of E. maxima leads to complete protection to challenge with the homologous parasite, but to complete escape of the heterologous H strain, i.e. the W strain induces an exquisitely strain-specific protective immune response with respect to the H strain. This dichotomy of survival in the face of immune-mediated killing has been examined further and, notably, mating between a drug-resistant W strain and a drug-sensitive H strain leads to recombination between the genetic loci responsible for the specificity of protective immunity and resistance to the anticoccidial drug robenidine. Such a finding opens the way forward for genetic mapping of the loci responsible for the induction of protective immunity and integration with the genome sequencing efforts.

show abstract

Arprinocid, an inhibitor of hypoxanthine- guanine transport

Cited by 17 publications

References 17 publications

A Genetic Linkage Map of the Apicomplexan Protozoan Parasite Eimeria tenella

A Genetic Linkage Map of the Apicomplexan Protozoan Parasite Eimeria tenella

Factors influencing the assessment of anticoccidial activity in cell culture

Integrating genetics and genomics to identify new leads for the control ofEimeriaspp.

Contact Info

Product

Resources

About