RESUMEN
A number of studies confirmed the involvement of transient receptor potential vanilloid (TRPV) and acid-sensing (ASIC) ion channels in the physiological processes associated with the development of anxiety disorders. This makes their ligands new potential anxiolytic agents. We examined the efficacy of two peptides from the sea anemone Heteractis crispa, Hcr 1b-2 and HCRG21, affecting ASIC1a and TRPV1 channels, respectively, in the open field and elevated plus maze tests. According to the obtained data, HCRG21 significantly decreases both the level of anxiety and stimulates the activity of animals at doses of 0.01-1 mg/kg, whereas Hcr 1b-2 has a weak anxiolytic effect only at a dose of 0.1 mg/kg. The pharmacodynamic study showed that the HCRG21 has an anxiolytic effect for 2 h, and its effectiveness is higher than that of the reference drug.
Asunto(s)
Ansiolíticos , Anémonas de Mar , Canales Iónicos Sensibles al Ácido , Animales , Ansiolíticos/farmacología , Péptidos/farmacología , Canales Catiónicos TRPVRESUMEN
The use of a high-fat diet, along with streptozotocin administration, can provide more profound insight into the mechanism of development of complications in diabetes, as well as their treatment. High-fat diet given over 3 weeks before intraperitoneal injection of streptozotocin in a dose of 40 mg/kg promoted the appearance of hyperglycemia in Wistar rats. The biochemical analysis of blood serum revealed increased levels of urea, triglycerides, cholesterol, AST, ALT, and concentration of inorganic phosphates and K+ ions in the high-fat diet group in comparison with the control. Both the biochemical analysis of the blood and histological analysis showed more pronounced abnormalities in rats receiving high-fat diet in comparison with animals receiving standard ration. These changes are the early markers for the development of nephropathy, impaired liver function, and microvascular disorders typical of patients with diabetes mellitus.
Asunto(s)
Diabetes Mellitus Experimental , Animales , Glucemia , Diabetes Mellitus Experimental/tratamiento farmacológico , Dieta Alta en Grasa/efectos adversos , Humanos , Ratas , Ratas Wistar , EstreptozocinaRESUMEN
The ion channel TRPV1, which is one of the most important integrators of pain and inflammatory stimuli, is considered a promising therapeutic target in the treatment of pain conditions. In this work, we performed a comparative study of the analgesic effect in the "hot plate" test of recombinant analogues of Kunitz-type peptides from the sea anemone Heteractis crispa venom: APHC1-modulator of TRPV1 and HCRG21-a full blocker of TRPV1. As a result of biological tests, it was shown that the full blocker HCRG21, despite the higher value of 50% effective concentration of TRPV1 inhibition, had an equal analgesic ability with the APHC1 upon intramuscular administration and retained it for 13 h of observation. The analgesic effect of APHC1 at a dose of 0.1 mg/kg when administered intramuscularly developed very quickly in 5 min but lasted 3 h. The differences in the pharmacodynamic profile of the peptides are in good agreement with different mechanisms of binding to TRPV1.
Asunto(s)
Analgésicos/farmacología , Venenos de Cnidarios/farmacología , Dolor/tratamiento farmacológico , Péptidos/farmacología , Canales Catiónicos TRPV/antagonistas & inhibidores , Secuencia de Aminoácidos , Analgésicos/administración & dosificación , Animales , Venenos de Cnidarios/administración & dosificación , Modelos Animales de Enfermedad , Calor , Inyecciones Intramusculares , Ratones , Ratones Endogámicos ICR , Dolor/metabolismo , Péptidos/administración & dosificación , Anémonas de Mar , Homología de SecuenciaRESUMEN
Recombinant analogue of the sea anemone Heteractismagnifica peptide was obtained, and the kinetic parameters of its interaction with mammalian α-amylases were determined. Magnificamide inhibits α-amylases significantly stronger than the medical drug acarbose (PrecoseTM or GlucobayTM). Magnificamide is assumed to find application as a drug for prevention and treatment of metabolic disorders and type 2 diabetes mellitus.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Péptidos/farmacología , alfa-Amilasas/antagonistas & inhibidores , Secuencia de Aminoácidos , Animales , Inhibidores Enzimáticos/química , Péptidos/química , Anémonas de Mar/químicaAsunto(s)
Analgésicos/farmacología , Péptidos/farmacología , Anémonas de Mar , Secuencia de Aminoácidos , Animales , Animales no Consanguíneos , Modelos Animales de Enfermedad , Calor , Inyecciones Intraperitoneales , Ratones , Datos de Secuencia Molecular , Dolor/tratamiento farmacológico , Péptidos/genética , Proteínas Recombinantes/farmacología , Anémonas de Mar/genética , Homología de Secuencia de AminoácidoRESUMEN
The anti-inflammatory effect of the recombinant polypeptide HCGS 1.20, a Kunitz-type serine protease inhibitor of the sea anemone Heteractis crispa, was investigated. It was shown that the polypeptide inhibits the increase of the concentration of calcium ions in mouse bone marrow derived macrophages elicited by histamine, and reduces the content of NO in lipopolysaccharide stimulated macrophages. A presumable mechanism of anti-inflammatory action of the polypeptide was being discussed.