RESUMO
AIMS AND BACKGROUND: Nausea and vomiting occur in the majority of patients receiving cisplatin (CDDP) chemotherapy. Ondansetron, a new 5-HT3 receptor antagonist, has been used effectively to control CDDP-induced nausea and vomiting. This study examined the potential of ondansetron to interfere with CDDP antitumor activity and toxicity in Ehrlich ascites carcinoma (EAC). METHODS: The influence of ondansetron on CDDP cytotoxicity was evaluated using EAC cells in culture. In addition, the influence of ondansetron pretreatment on CDDP-induced antitumor activity and host tissue toxicity was studied in EAC-bearing mice. RESULTS: Ondansetron (0.25 microM) enhanced CDDP (0-32 microM) cytotoxicity against EAC cells in vitro. In EAC-bearing mice ondansetron (0.2 mg/kg,ip) administered 1 h before CDDP (7 mg/kg, ip) did not modify the antitumor activity of CDDP. CDDP (7 mg/kg, ip) single treatment induced significant increases in blood urea nitrogen (2-fold) and serum creatinine (2.5-fold) and significant decreases in hematocrit (25%) and white blood cell count (39%) compared to saline treatment. Mice receiving ondansetron 1 h before CDDP showed no significant enhancement of CDDP-induced nephrotoxicity or myelosuppression compared to those pretreated with saline receiving the same dose of CDDP. CONCLUSIONS: This study suggests that the use of ondansetron to control CDDP-induced nausea and vomiting does not affect CDDP antitumor efficacy.
Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Cisplatino/farmacologia , Náusea/prevenção & controle , Ondansetron/uso terapêutico , Vômito/prevenção & controle , Análise de Variância , Animais , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Camundongos , Náusea/induzido quimicamente , Células Tumorais Cultivadas , Vômito/induzido quimicamenteRESUMO
Short-term and long-term effects of bromocriptine mesylate (10 mg/kg i.p.) on cyclic AMP contents of the liver and some endocrine glands have been investigated in the presence and absence of sulpiride (10 mg/kg i.p.). Results revealed that bromocriptine caused significant elevations in the cyclic AMP contents of the liver and reduction in its adrenocortical content. Bromocriptine effect on the adrenal cortex was antagonized by sulpiride, whereas its effect on the liver was not changed. Bromocriptine did not change the cyclic AMP content in the thyroid gland or the ovary.
Assuntos
Bromocriptina/farmacologia , AMP Cíclico/metabolismo , Glândulas Endócrinas/metabolismo , Receptores Dopaminérgicos/metabolismo , Sulpirida/farmacologia , Córtex Suprarrenal/efeitos dos fármacos , Córtex Suprarrenal/metabolismo , Animais , Interações Medicamentosas , Glândulas Endócrinas/efeitos dos fármacos , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ratos , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores de Dopamina D2 , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Fatores de TempoRESUMO
Cyclic GMP contents of the thyroid gland and ovary were significantly increased in response to single and multiple treatments of bromocriptine, an effect which was antagonized by sulpiride. Liver and adrenocortical cyclic GMP levels have not been changed by bromocriptine although sulpiride alone induced a significant reduction. The data may indicate the presence of D2 receptors in ovary and thyroid gland that are related to cyclic GMP.
Assuntos
Córtex Suprarrenal/metabolismo , Bromocriptina/farmacologia , GMP Cíclico/metabolismo , Fígado/metabolismo , Ovário/metabolismo , Glândula Tireoide/metabolismo , Córtex Suprarrenal/efeitos dos fármacos , Animais , Feminino , Fígado/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ratos , Sulpirida/farmacologia , Glândula Tireoide/efeitos dos fármacosRESUMO
The dopaminergic drug bromocriptine inhibited the release of insulin from isolated mouse pancreatic islets. The effect was counteracted by haloperidol or pimozide. It is suggested that insulin release may be inhibited through activation of D-2 dopaminergic receptors in the pancreatic beta-cells.
Assuntos
Bromocriptina/farmacologia , Insulina/metabolismo , Animais , Haloperidol/farmacologia , Técnicas In Vitro , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Camundongos , Pimozida/farmacologia , Receptores Dopaminérgicos/efeitos dos fármacosRESUMO
The effect of adenosine in insulin secretion and adenylate cyclase activity of rat islets of Langerhans was investigated. Adenosine inhibited insulin secretion stimulated by glucose, glucagon, prostaglandin E2, tolbutamine and theophylline. Adenosine decreased basal adenylate cyclase activity of the islets as well as that stimulated by glucagon prostaglandin E2 and GTP, although fluoride-stimulated activity was not affected. Neither insulin secretion nor adenylate cyclase activity of the islets was affected by adenine, AMP or ADP. The inhibitory effect of adenosine on adenylate cyclase activity was not altered by either phenoxybenzamine (alpha-adrenergic blocker) or propranolol (beta-adrenergic blocker), suggesting that the effect is not mediated through the adrenergic receptors of the islet cells. These results suggest that the intracellular concentration of adenosine in the beta-cell may play a role in regulating insulin secretion and that this effect may be mediated via alterations in the activity of adenylate cyclase in the beta-cell.
