RESUMEN
The data available to date indicate that the activation of nicotinic acetylcholine receptors (nAChR) of α7 type can reduce heart damage resulting from ischemia and subsequent reperfusion. We have studied two new synthetic D-analogs of 6-bromohypaphorine, which are selective agonists of α7 nAChR, in a rat model of myocardial ischemia. Acute myocardial infarction in animals was induced by occlusion of the left coronary artery with its subsequent reperfusion under mechanical lung ventilation. It was found that one of the analogs was more active, and treatment with it at the onset of reperfusion statistically reduced infarct size. This analog also prevented changes in the concentration of potassium and sodium ions in the blood, occurring during occlusion/reperfusion injury. The data obtained indicate that hypaphorine analogs are promising for the development of drugs that reduce the adverse effects of myocardial infarction.
Asunto(s)
Lesiones Cardíacas , Infarto del Miocardio , Isquemia Miocárdica , Daño por Reperfusión Miocárdica , Receptores Nicotínicos , Animales , Infarto del Miocardio/tratamiento farmacológico , Isquemia Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , Ratas , Reperfusión , Triptófano/análogos & derivadosRESUMEN
We studies the receptor-binding specificity of the synthetic peptide HAP (High Affinity Peptide) and its analogues, which are regarded as a model of the orthosteric site nicotinic acetylcholine receptors (nAChR). Using radioligand analysis, electrophysiology tests, and calcium imaging, we assessed the ability of HAP to interact with nAChR antagonists: long α-neurotoxins and α-conotoxins. A high affinity of HAP for α-bungarotoxin and the absence of its interaction with α-cobratoxin and α-conotoxins was found. The synthesized analogues of HAP in general retained the properties of the original peptide. Thus, HAP cannot be a model of a ligand-binding site.
Asunto(s)
Colinérgicos/farmacología , Fragmentos de Péptidos/metabolismo , Receptores Nicotínicos/metabolismo , Animales , Sitios de Unión , Bungarotoxinas/farmacología , Calcio/metabolismo , Línea Celular , Conotoxinas/metabolismo , Conotoxinas/farmacología , Humanos , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Ratones , Modelos Moleculares , Neurotoxinas/metabolismo , Neurotoxinas/farmacología , Oocitos , Técnicas de Placa-Clamp , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/química , Biblioteca de Péptidos , Ensayo de Unión Radioligante , Ratas , Receptores Nicotínicos/química , Receptores Nicotínicos/genética , Torpedo , Imagen de Colorante Sensible al Voltaje , Xenopus laevisRESUMEN
Nonconventional three-finger toxin BMLCL was isolated from B. multicinctus venom, and its interaction with different subtypes of nicotinic acetylcholine receptor (nAChR) was studied. It was found that BMLCL is able to interact with high efficiency with both α7 and muscle type nAChRs.