RESUMEN
In the present study we investigated the role of 5-hydroxytryptamine (5-HT) and 5-HT1A receptor during liver regeneration after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in male Wistar rats. 5-HT content was significantly increased during liver regeneration after PH and NDEA induced hepatocellular carcinoma. Scatchard analysis using 8-OH-DPAT, a 5-HT1A specific agonist showed a decreased receptor during liver regeneration after PH and NDEA induced hepatocellular carcinoma. 5-HT when added alone to primary hepatocyte culture did not increase DNA synthesis but was able to increase the EGF mediated DNA synthesis and inhibit the TGF beta 1 mediated DNA synthesis suppression in vitro. This confirmed the co-mitogenic activity of 5-HT. 8-OH-DPAT at a concentration of 10(-4) M inhibited the basal and EGF-mediated DNA synthesis in primary hepatocyte cultures. It also suppressed the TGF beta 1-mediated DNA synthesis suppression. This clearly showed that activated 5-HT1A receptor inhibited hepatocyte DNA synthesis. Our results suggest that decreased hepatic 5-HT1A receptor function during hepatocyte regeneration and neoplasia has clinical significance in the control of cell proliferation.
Asunto(s)
Neoplasias Hepáticas Experimentales/metabolismo , Regeneración Hepática/fisiología , Receptor de Serotonina 5-HT1A/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Carcinógenos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Cromatografía Líquida de Alta Presión , ADN de Neoplasias/biosíntesis , ADN de Neoplasias/genética , Dietilnitrosamina , Factor de Crecimiento Epidérmico/farmacología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Neoplasias Hepáticas Experimentales/inducido químicamente , Masculino , Ratas , Ratas Wistar , Serotonina/metabolismo , Agonistas de Receptores de Serotonina/farmacología , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
The brain neurotransmitters' receptor activity and hormonal pathways control many physiological functions in the body. Acetylcholine (ACh), a major neurotransmitter from autonomic nervous system, regulates the cholinergic stimulation of insulin secretion, through interactions with muscarinic receptors. The objective of the present study was to investigate the changes in the total muscarinic and muscarinic M1 receptor ([(3)H]quinuclidinyl benzilate; QNB) binding and gene expression in the hypothalamus, brainstem, and pancreatic islets of streptozotocin (STZ)-induced diabetic and insulin-treated diabetic rats. In the hypothalamus and brainstem, total muscarinic receptor numbers were increased in diabetic rats with increase in affinity. Hypothalamic and brainstem muscarinic M1 receptors number were decreased in STZ diabetic rats with increase in affinity. In the pancreatic islets, muscarinic M1 receptors of diabetic rats were decreased, with a decrease in affinity. In all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR data also showed a decrease in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. Thus our results suggest that insulin modulates binding parameters and gene expression of total and muscarinic M1 receptors.
Asunto(s)
Tronco Encefálico/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hipotálamo/metabolismo , Islotes Pancreáticos/metabolismo , Receptor Muscarínico M1/biosíntesis , Animales , Glucemia/efectos de los fármacos , Tronco Encefálico/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Expresión Génica/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Insulina/uso terapéutico , Islotes Pancreáticos/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Receptor Muscarínico M1/efectos de los fármacos , Receptor Muscarínico M1/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The present study was to investigate the role of central 5-HT and 5-HT(1A) receptor binding and gene expression in a rat model of pancreatic regeneration using 60% pancreatectomy. The pancreatic regeneration was evaluated by 5-HT content and 5-HT(1A) receptor gene expression in the cerebral cortex (CC) and brain stem (BS) of sham operated, 72 h and 7 days pancreatectomised rats. 5-HT content significantly increased in the CC (P < 0.01) and BS (P < 0.05) of 72 h pancreatectomised rats. Sympathetic activity was decreased as indicated by the significantly decreased norepinephrine (NE) and epinephrine (EPI) level (P < 0.001 and P < 0.05) in the plasma of 72 h pancreatectomised rats. 5-HT(1A) receptor density and affinity was decreased in the CC (P < 0.01) and BS (P < 0.01). These changes correlated with a diminished 5-HT(1A) receptor mRNA expression in the brain regions studied. Our results suggest that the brain 5-HT through 5-HT(1A) receptor has a functional role in the pancreatic regeneration through the sympathetic regulation.