RESUMO
The injection of a dopamine D(2) receptor hammerhead ribozyme (20 microg) once daily for 5 days into the nucleus accumbens of rats resulted in an inhibition of stereotyped sniffing and locomotor activation produced by the selective dopamine D(2) receptor agonist, quinpirole (0.4 mg kg(-1) s.c.). The results suggest that ribozymes may be useful in the study of in vivo gene function in the brain.
Assuntos
Agonistas de Dopamina/farmacologia , Quimpirol/antagonistas & inibidores , RNA Catalítico/farmacologia , Receptores de Dopamina D2/metabolismo , Comportamento Estereotipado/efeitos dos fármacos , Animais , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/farmacologia , Injeções , Masculino , Atividade Motora/efeitos dos fármacos , Núcleo Accumbens , Quimpirol/farmacologia , Ratos , Ratos Sprague-Dawley , Sulpirida/administração & dosagem , Sulpirida/farmacologiaRESUMO
The rat Chromosome (Chr) 2 harbors several genes controlling tumor growth or development, blood pressure, and non-insulin-dependent diabetes mellitus. We report that the region (2q1) containing the mammary susceptibility cancer gene Mcs1 also harbors the genes encoding cyclin B1, interleukin 6 signal transducer (gp130), and proprotein convertase 1. We also generated 13 new anonymous microsatellite markers from Chr 2-sorted DNA. These markers, as well as a microsatellite marker in the cyclin B1 gene, were genetically mapped in combination with known markers. A cyclin B1-related gene was also cytogenetically assigned to rat Chr 11q22-q23.
Assuntos
Antígenos CD/genética , Ciclina B/genética , Glicoproteínas de Membrana/genética , Repetições de Microssatélites , Pró-Proteína Convertases , Proteínas de Saccharomyces cerevisiae , Subtilisinas/genética , Animais , Mapeamento Cromossômico , Ciclina B1 , Receptor gp130 de Citocina , Ligação Genética , Hibridização in Situ Fluorescente , RatosRESUMO
Insufficient efficacy and/or specificity of antisense oligonucleotides limit their in vivo usefulness. We demonstrate here that a high-affinity DNA analog, locked nucleic acid (LNA), confers several desired properties to antisense agents. Unlike DNA, LNA/DNA copolymers were not degraded readily in blood serum and cell extracts. However, like DNA, the LNA/DNA copolymers were capable of activating RNase H, an important antisense mechanism of action. In contrast to phosphorothioate-containing oligonucleotides, isosequential LNA analogs did not cause detectable toxic reactions in rat brain. LNA/DNA copolymers exhibited potent antisense activity on assay systems as disparate as a G-protein-coupled receptor in living rat brain and an Escherichia coli reporter gene. LNA-containing oligonucleotides will likely be useful for many antisense applications.