Uroguanylin induces electroencephalographic spikes in rats

Abstract

Uroguanylin (UGN) is an endogenous peptide that acts on membrane-bound guanylate cyclase receptors of intestinal and renal cells increasing cGMP production and regulating electrolyte and water epithelial transport. Recent research works demonstrate the expression of this peptide and its receptor in the central nervous system. The current work was undertaken in order to evaluate modifications of electroencephalographic spectra (EEG) in anesthetized Wistar rats, submitted to intracisternal infusion of uroguanylin (0.0125 nmoles/min or 0.04 nmoles/min). The current observations demonstrate that 0.0125 nmoles/min and 0.04 nmoles/min intracisternal infusion of UGN significantly enhances amplitude and frequency of sharp waves and evoked spikes (p = 0.03). No statistical significance was observed on absolute alpha and theta spectra amplitude. The present data suggest that UGN acts on bioelectrogenesis of cortical cells by inducing hypersynchronic firing of neurons. This effect is blocked by nedocromil, suggesting that UGN acts by increasing the activity of chloride channels.Keywords: neuroexcitatory response, brain spikes, neuronal depolarization. Uroguanilina induz potenciais em espiga no eletroencefalograma de ratos ResumoA uroguanilina (UGN) é um peptídeo endógeno que age em receptores do tipo guanilato ciclase de membrana de células intestinais e renais aumentando a produção de GMPc e regulando o transporte epitelial de eletrólitos e água. Pesquisas recentes demonstraram a expressão deste peptídeo e de seus receptores no sistema nervosa central. O presente trabalho foi realizado com objetivo de avaliar possíveis mudanças no espectro do eletroencefalograma (EEG) de ratos Wistar anestesiados, submetidos à infusão intracisternal de uroguanilina (0.0125 nmoles/min or 0.04 nmoles/min). Os resultados apresentados no corrente trabalho demonstram que a infusão intracisternal de ambas as doses de UGN aumenta significativamente a amplitude e frequência das espículas (p = 0.03). Não foram encontradas diferenças estatísticas na amplitude absoluta dos espectros alfa ou teta. Os dados apresentados neste trabalho mostram que a UGN age na bioeletrogênese de células corticais induzindo disparo hipersincrônico de neurônios. Este efeito é bloqueado por nedocromil, sugerindo que UGN atua pelo aumento de atividade de canais de cloreto.Palavras-chave: neuroexcitação, cerebral spikes, despolarização neuronal.

Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities

“…There are two discrete neuronal circuits expressing GC-C reported in the literature, one originating in the tyrosine hydroxylase negative neurons of the ventral pre-mammillary nucleus (PMV) in the hypothalamus and the second in the tyrosine hydroxylase positive neurons of the ventral tegmental area (VTA) and substantia nigra (SN) in the midbrain, both of which independently project to other sites throughout the brain ( 18 ). In neurons, GC-C may play a role in ion fluxes across the plasma membrane, coordinating neuronal activity and interactions between neurons ( 135 ). Interestingly, recent research has identified two distinct uroguanylin signaling mechanisms in the brain: a GC-C dependent pathway that hyperpolarized neurons (Purkinje cells of the cerebellum) and a GC-C independent pathway that increased calcium levels in astrocytes ( 136 ).…”