RESUMO
The pharmacological actions of lithium and magnesium have been investigated using isolated smooth muscle preparations from the rat gastrointestinal tract. Tissue contraction was evoked by means of carbachol or electrical field stimulation and the degree of inhibition of contraction caused by lithium was measured. Lithium effects were compared with those of the chemically similar ions, magnesium and calcium, by manipulation of the physiological buffer solutions. Lithium antagonism was enhanced when tissue contractile mechanisms were dependent on extracellular calcium concentration in the bathing fluid. This suggests that lithium is acting at the cell membrane by preventing calcium entry via ion channels. These results are consistent with evidence from clinical studies which indicate low cellular accumulation of lithium at therapeutic concentrations.
Assuntos
Carbacol/antagonistas & inibidores , Sistema Digestório/efeitos dos fármacos , Lítio/farmacologia , Magnésio/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Animais , Cálcio/farmacocinética , Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Colo/efeitos dos fármacos , Sistema Digestório/metabolismo , Estimulação Elétrica , Feminino , Fundo Gástrico/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
A novel technique utilizing samples of human distal ileum removed at surgery was used to study magnesium (Mg) absorption. Specimens of isolated absorptive mucosa were obtained by careful dissection of the tissue to remove the muscle layers, and were mounted in flux chambers. Mean tissue Mg concentration in human isolated intestinal mucosa was found to be within the postulated normal range for human tissue. Mucosal to serosal Mg transport was unaffected by ouabain or 2,4-dinitrophenol and sodium fluoride. Overall, the data indicate Mg absorption in distal ileum to be passive in nature, although a minor active transcellular component cannot be excluded.
Assuntos
Íleo/metabolismo , Absorção Intestinal , Mucosa Intestinal/metabolismo , Magnésio/farmacocinética , 2,4-Dinitrofenol , Adolescente , Adulto , Transporte Biológico/efeitos dos fármacos , Técnicas de Cultura , Dinitrofenóis/farmacologia , Feminino , Humanos , Íleo/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Pessoa de Meia-Idade , Ouabaína/farmacologia , Fluoreto de Sódio/farmacologia , Desacopladores/farmacologiaRESUMO
A method that allows the quantitative assessment of ileal mucosal cell uptake and transport of bile acids in mucosal biopsy specimens has been validated. Viability of the tissue was confirmed by maintenance of normal cell morphology, wet weight, extracellular space, porosity to polyethylene glycol-900, lactate dehydrogenase release, and transmucosal potential difference. Using 14C-taurocholic acid, absorption was shown to be directional, capable of working against a concentration gradient, reduced by metabolic inhibitors, and sodium dependent. The system showed saturation kinetics with an estimated Km of 10 mumol/l. At a standard substrate concentration of 10 mumol/l ileal mucosal bile acid absorption was compared in patients with colorectal cancer (n = 6), ulcerative colitis (n = 10), and slow transit constipation (n = 8). There was no significant difference in tissue uptake or transport between the three groups.