Assuntos
Claviceps/fisiologia , Alcaloides de Claviceps/biossíntese , Acetilcoenzima A/metabolismo , Catálise , Divisão Celular , Claviceps/citologia , Claviceps/genética , Meios de Cultura/metabolismo , Ergolinas/biossíntese , Alcaloides de Claviceps/antagonistas & inibidores , Alcaloides de Claviceps/síntese química , Ácido Lisérgico/metabolismo , Biossíntese Peptídica , Triptofano/metabolismoRESUMO
The effects of several ergot alkaloid derivatives on the concentration of cyclic AMP in intact rabbit retinae were investigated in vitro. All compounds were found to be potent inducers of cyclic AMP production, half-maximal stimulation being obtained at 10(-6)M, and maximal stimulation at 10(-4)M concentrations. The range of effective concentrations was very well comparable with that of dopamine (or apomorphine) in the same experimental conditions. Furthermore, the accumulation of cyclic AMP induced by the ergot derivatives was blocked by fluphenazine, at 10(-4)-5 X 10(-4)M, or lithium, at 5 X 10(-2)M concentrations. Both antipsychotic drugs were found to be very potent inhibitors of dopamine-(or apomorphine-) induced production of cyclic AMP in the same preparation. A potential dopamine-mimetic activity of ergot derivatives (or of other dopamine-like drugs) can be specifically tested on isolated rabbit retinae in vitro, either before undertaking experiments in vivo or in correlation with behavioural studies.
Assuntos
AMP Cíclico/biossíntese , Dopamina/farmacologia , Alcaloides de Claviceps/farmacologia , Retina/metabolismo , Animais , Apomorfina/farmacologia , Relação Dose-Resposta a Droga , Ergolinas/farmacologia , Ergonovina/farmacologia , Alcaloides de Claviceps/antagonistas & inibidores , Flufenazina/farmacologia , Lítio/farmacologia , CoelhosAssuntos
Antagonistas de Dopamina , Alcaloides de Claviceps/antagonistas & inibidores , Fenotiazinas/farmacologia , Receptores de Droga , Ligação Competitiva , Dopamina/metabolismo , Alcaloides de Claviceps/metabolismo , Dietilamida do Ácido Lisérgico/antagonistas & inibidores , Dietilamida do Ácido Lisérgico/metabolismo , Modelos Estruturais , Conformação Molecular , Fenotiazinas/metabolismo , Relação Estrutura-AtividadeAssuntos
Dopamina/farmacologia , Alcaloides de Claviceps/farmacologia , Lobo Parietal/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Animais , Clorpromazina/farmacologia , Antagonistas de Dopamina , Alcaloides de Claviceps/antagonistas & inibidores , Iontoforese , Masculino , Norepinefrina/farmacologia , Ratos , Serotonina/farmacologiaAssuntos
Circulação Sanguínea/efeitos dos fármacos , Alcaloides de Claviceps/farmacologia , Ergotamina/farmacologia , Anormalidades Induzidas por Medicamentos , Administração Oral , Alcaloides/toxicidade , Animais , Cães , Sinergismo Farmacológico , Epinefrina/farmacologia , Alcaloides de Claviceps/administração & dosagem , Alcaloides de Claviceps/antagonistas & inibidores , Ergotamina/administração & dosagem , Feminino , Cobaias , Átrios do Coração/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Íleo/efeitos dos fármacos , Técnicas In Vitro , Injeções Intravenosas , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Nicotina/antagonistas & inibidores , Norepinefrina/farmacologia , Pentobarbital/farmacologia , Coelhos , Ratos , Glândulas Seminais/efeitos dos fármacos , Especificidade da Espécie , Útero/efeitos dos fármacosRESUMO
The failure of l-leucine to stimulate ergot alkaloid production in a synthetic medium indicates that the previously observed stimulation by tryptophan and tryptophan analogues does not merely represent a nutritional effect. Tryptophan, but not mevalonate or 5-methyltryptophan, is able to overcome the inhibition of alkaloid synthesis by high levels of inorganic phosphate. Therefore, high phosphate levels seem to limit the synthesis of tryptophan; they may, in addition, prevent induction of alkaloid synthesis by preventing accumulation of tryptophan. Experiments which indicate a 2- to 3-fold temporary increase of intracellular free tryptophan and a 20- to 25-fold increase of tryptophan synthetase activity during the transition period between growth and alkaloid production phase are in agreement with the previously postulated induction of alkaloid synthesis by tryptophan. The latter experiments also indicate 4- to 6-fold repression of this enzyme by tryptophan.
