RESUMO
The effect of anti-tissue antisera on the contractile response of isolated smooth muscle cells from rabbit antrum has been investigated. Anti-stomach (SAE), anti-colon (SAC) and anti-diencephale (SAD) antisera induced a dose-dependent contraction is isolated cells, whereas both non-immune serum and antisera obtained by immunization with other foetal tissues were ineffective. Proglumide, the well known gastrin antagonist, similarly inhibited both gastrin- and SAE, SAC, SAD antisera-induced contraction of isolated smooth muscle cells.
Assuntos
Soros Imunes/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Animais , Colo/imunologia , Diencéfalo/imunologia , Relação Dose-Resposta a Droga , Soros Imunes/administração & dosagem , Músculo Liso/citologia , Proglumida/farmacologia , Antro Pilórico/citologia , Coelhos , Estômago/imunologiaRESUMO
The unnatural d diastereoisomer at carbon 6 of 5-methyltetrahydrofolate was only slightly less effective than the natural 1 diastereoisomer as a competitive inhibitor of the carrier-mediated membrane transport of [3H]methotrexate into L1210 murine leukemia cells. The apparent Ki for a mixture containing equal amounts of both natural and unnatural diastereoisomers was not significantly different from that found for the unnatural form. These results show that the reduced folate carrier system in these cells has a strong affinity for the unnatural stereoisomer, a finding in contrast to that obtained with the corresponding diastereoisomer of 5-formyltetrahydrofolate.
Assuntos
Leucemia L1210/metabolismo , Metotrexato/metabolismo , Tetra-Hidrofolatos/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Membrana Celular/metabolismo , Camundongos , EstereoisomerismoAssuntos
Formiltetra-Hidrofolatos/farmacologia , Metotrexato/antagonistas & inibidores , Tetra-Hidrofolatos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Cinética , Leucemia L1210/metabolismo , Metotrexato/metabolismo , Camundongos , Camundongos Endogâmicos , Conformação Molecular , Estereoisomerismo , Relação Estrutura-Atividade , Fatores de TempoRESUMO
1. The concentrations of folate-dependent enzymes in Neurospora crassa Lindegren A wild type (FGSC no. 853), Ser-l mutant, strain H605a (FGSC no. 118), and for mutant, strain C-24 (FGSC no. 9), were compared during exponential growth on defined minimal media. Both mutants were partially lacking in serine hydroxymethyltransferase, but contained higher concentrations of 10-formyltetrahydrofolate synthetase than did the wild type. Mycelia of the mutants contained higher concentrations of these enzymes when growth media were supplemented with 1mM-glycine. In the wild-type, this glycine supplement also increased the specific activities of 5,10-methylenetetrahydrofolate dehydrogenase and 5,10-methylenetetrahydrofolate reductase. 5. During growth, total folate and polyglutamyl folate concentrations were greatest in the wild-type. Methylfolates were not detected in mutant Ser-l, and were only present in the for mutant after growth in glycine-supplemented media. Exogenous glycine increased folate concentration threefold in the wild type, mainly owing to increases in unsubstituted polyglutamyl derivatives. 3. Feeding experiments using 14C-labelled substrates showed that C1 units were generated from formate, glycine and serine in the wild type. Greater incorporation of 14C occurred when mycelia were cultured in glycine-supplemented media. Formate and serine were precursors of C1 units in the mutants, but the ability to cleave glycine was slight or lacking.