Altered content and modulation of soluble guanylate cyclase in the cerebellum of rats with portacaval anastomosis.
It is shown that the glutamate-NO-cGMP pathway is impaired in cerebellum of rats with portacaval anastomosis in vivo as assessed by in vivo brain microdialysis in freely moving rats. NMDA-induced increase in extracellular cGMP in the cerebellum was significantly reduced (by 27%) in rats with portacaval anastomosis. Activation of soluble guanylate cyclase by the NO-generating agent S-nitroso-N-acetyl-penicillamine and by the NO-independent activator YC-1 was also significantly reduced (by 35-40%), indicating that portacaval anastomosis leads to remarkable alterations in the modulation of guanylate cyclase in cerebellum. Moreover, the content of soluble guanylate cyclase was increased ca. two-fold in the cerebellum of rats with portacaval anastomosis. Activation of soluble guanylate cyclase by NO was higher in lymphocytes isolated from rats with portacaval anastomosis (3.3-fold) than in lymphocytes from control rats (2.1-fold). The results reported show that the content and modulation of soluble guanylate cyclase are altered in brain of rats with hepatic failure, resulting in altered function of the glutamate-NO-cGMP pathway in the rat in vivo. This may lead to alterations in cerebral processes such as intercellular communication, circadian rhythms, including the sleep-waking cycle, long-term potentiation, and some forms of learning and memory.
Monfort
P
P
Laboratory of Neurobiology, Instituto de Investigaciones Citologicas, Fundación Valenciana de Investigaciones Biomédicas, Amadeo de Saboya 4, 46010 Valencia, Spain.
Corbalán
R
R
Martinez
L
L
López-Talavera
J
J
Córdoba
J
J
Felipo
V
V
D000818:Animals; D002531:Cerebellum / Q000201:enzymology* / Q000503:physiopathology; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D020536:Enzyme Activators / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000201:enzymology* / Q000503:physiopathology; D022124:Hyperammonemia / Q000150:complications / Q000201:enzymology / Q000503:physiopathology; D015151:Immunoblotting; D007191:Indazoles / Q000494:pharmacology; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine; D009435:Synaptic Transmission / Q000502:physiology
D020536:Enzyme Activators; D018690:Excitatory Amino Acid Agonists; D007191:Indazoles; D020030:Nitric Oxide Donors; D016194:Receptors, N-Methyl-D-Aspartate; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D026423:S-Nitroso-N-Acetylpenicillamine; D006162:Guanylate Cyclase; D010396:Penicillamine; D006152:Cyclic GMP