RESUMEN
Previously, we have shown that the endogenous neuropeptide cycloprolylglycine (CPG) is the positive modulator of AMPA receptors and revealed the dependence of its anxiolytic and antihypoxic action on BDNF/Trk signaling. In the present work, we for the first time conducted in vitro experiments using the AMPA receptor blockers DNQX and GYKI 52466 and the Trk receptor blocker K252a. It is shown that the neuroprotective effect of CPG depends on the activation of both AMPA and Trk receptors.
Asunto(s)
Neuropéptidos , Fármacos Neuroprotectores , Fármacos Neuroprotectores/farmacología , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico , Receptor trkB/metabolismo , Receptores AMPA , Factor Neurotrófico Derivado del Encéfalo/metabolismoRESUMEN
Previously we have shown that the neuropeptide cycloprolylglycine is an endogenous positive modulator of AMPA receptors and assumed that the pharmacological effects of CPG are associated with the brain neurotrophic factor. In this paper, we have first demonstrated that DNQX, an inhibitor of AMPA receptors, and K252A, an ihibitor of Trk receptors, prevented the anxiolytic effect of CPG, which confirms the formulated hypothesis.
Asunto(s)
Trastornos de Ansiedad/tratamiento farmacológico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Carbazoles/farmacología , Alcaloides Indólicos/farmacología , Glicoproteínas de Membrana/antagonistas & inhibidores , Péptidos Cíclicos/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Quinoxalinas/farmacología , Receptores AMPA/antagonistas & inhibidores , Animales , Ansiolíticos/farmacología , Trastornos de Ansiedad/metabolismo , Trastornos de Ansiedad/patología , Inhibidores Enzimáticos/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Masculino , Ratones , Ratones Endogámicos BALB C , Péptidos Cíclicos/químicaRESUMEN
It was shown for the first time that the endogenous cyclic dipeptide cycloprolylglycine (CPG) at concentrations of 10(-7) and 10(-3) M and piracetam at a concentration of 10(-3) M increased the content of brainderived neurotrophic factor (BDNF) in the culture of neuronal cells in normal state and under conditions of glutamate and 6-oxydopamine neurotoxicity. This may indicate the possible involvement of BDNF in the mechanism of action of neuropeptide CPG and piracetam.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Péptidos Cíclicos/farmacología , Piracetam/farmacología , Animales , Línea Celular , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Ácido Glutámico/toxicidad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Ratones , Oxidopamina/toxicidad , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/metabolismoRESUMEN
We have previously shown that neuropeptide cycloprolylglycine (CPG) increases the content of brain-derived neurotrophic factor (BDNF) in the culture of neuronal cells under normal conditions and in pathology. This is the first study to show that CPG at a physiological concentration of 10-6 M significantly enhances the transmembrane AMPA currents in rat cerebellar Purkinje cells. Thus, CPG is a positive endogenous modulator of AMPA receptors. It was assumed that the neuropsychotropic effects of CPG are implemented as a result of BDNF accumulation after the activation of AMPA receptors by this neuropeptide.
