RESUMEN
Phytic acid, a constituent of various plants, has been related to health benefits. Phytic acid has been shown to inhibit purine nucleotide metabolism in vitro and suppress elevation of plasma uric acid levels after purine administration in animal models. This study investigated the effect of phytic acid on postprandial serum uric acid (SUA) in humans. This randomized, double-blind, crossover design study included 48 healthy subjects with normal fasting SUA. Subjects consumed a control drink and a phytic acid drink with purine-rich food, and serum and urine uric acid levels were measured for 360 min after purine loading. Phytic acid lowered the incremental area under the curve (0-360 min) and incremental maximum concentration of SUA after purine loading (p < 0.05); tended to lower cumulative urinary uric acid excretion (0-360 min) after purine loading (p < 0.10); and suppressed postprandial SUA in this clinical study. Altogether, our findings suggest that phytic acid may play a beneficial role in controlling postprandial SUA.
Asunto(s)
Ácido Fítico/sangre , Ácido Úrico/sangre , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Ácido Fítico/administración & dosificación , Purinas/administración & dosificación , Purinas/sangre , Adulto JovenRESUMEN
The mechanism by which NC-1900, a new pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH(2) (AVP(4-9)) analog, improves spatial memory in rats using an eight-arm radial maze was examined. Even at very low doses (0.2 ng/kg for s.c., 1 microg/kg for p.o., 1 fg for i.c.v.) NC-1900 improved scopolamine-induced impairment of spatial memory. NC-1900 (1 ng/kg, s.c.) also improved impairment of spatial memory induced by pirenzepine, a muscarinic(1) (M(1)) receptor antagonist, and by KN-62, a Ca2+/calmodulin (CaM)-dependent protein kinase II inhibitor. [Pmp(1), Tyr(Me)(2)]-Arg(8)-vasopressin, a vasopressin(1A) (V(1A)) receptor antagonist, and nicardipine, L-type Ca2+ blocker, but not OPC-31260, a V(2) antagonist, suppressed the effect of NC-1900 on scopolamine-induced impairment of spatial memory. A microdialysis study showed that NC-1900 did not affect acetylcholine release in the ventral hippocampus (VH) of intact rats or of scopolamine-treated rats. NC-1900 (1 microM) increased [Ca2+](i) in the VH than in the dorsal hippocampus (DH). Pretreatment with nicardipine (1 microM) and Ca2+ -free conditions inhibited the NC-1900-induced [Ca2+](i) response in the VH. Whereas co-administration of NC-1900 (1 microM) and carbachol (500 microM) increased [Ca2+](i) in the VH. Moreover, nicardipine concentration-dependently inhibited the increase in [Ca2+](i) induced by the co-administration of NC-1900 and carbachol in the VH. These results suggest that NC-1900 activates the V(1A) receptor at the postsynaptic cholinergic nerve, and causes a transient influx of intracellular Ca2+ through L-type Ca2+ channels, to interact with the M(1) receptor. The activation of these Ca2+ -dependent processes induced by NC-1900 may be involved in the positive effect of NC-1900 on scopolamine-induced impairment of spatial memory.
Asunto(s)
1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Nootrópicos/farmacología , Oligopéptidos/farmacología , Receptores de Vasopresinas/efectos de los fármacos , Escopolamina/farmacología , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Animales , Antagonistas de los Receptores de Hormonas Antidiuréticas , Benzazepinas/farmacología , Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo L/efectos de los fármacos , Proteínas Quinasas Dependientes de Calcio-Calmodulina/antagonistas & inhibidores , Antagonistas Colinérgicos/farmacología , Microdiálisis , Nicardipino/farmacología , Pirenzepina/farmacología , Ácido Pirrolidona Carboxílico/análogos & derivados , Ratas , Ratas Wistar , Receptores de Vasopresinas/fisiologíaRESUMEN
In order to clarify the mechanism by which pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH(2) (vasopressin-(4-9)), a major metabolite C-terminal fragment of [Arg(8)]-vasopressin (vasopressin-(1-9)), improves learning and memory, we used several different drugs such as an acetylcholine receptor antagonist, a Ca(2+)/calmodulin-dependent protein kinase II inhibitor, vasopressin receptor antagonists and L-type Ca(2+) channel blocker to disrupt spatial memory in rats. Moreover, we examined the effect of vasopressin-(4-9) on acetylcholine release in the ventral hippocampus using microdialysis. Vasopressin-(4-9) (10 fg/brain, i.c.v.) improved the impairment of spatial memory in the eight-arm radial maze induced by scopolamine, pirenzepine and Ca(2+)/calmodulin -dependent protein kinase II inhibitor. Pirenzepine, a vasopressin V(1A) receptor antagonist, and L-type Ca(2+) channel blocker, but not a vasopressin V(2) receptor antagonist, suppressed the effects of vasopressin-(4-9) on scopolamine-induced impairment of spatial memory. Moreover, vasopressin-(4-9) did not affect acetylcholine release in the ventral hippocampus of intact rats or of scopolamine-treated rats as assessed by microdialysis. These results suggest that vasopressin-(4-9) activates vasopressin V(1A) receptors on the postsynaptic membrane of cholinergic neurons, and induces a transient influx of intracellular Ca(2+) through L-type Ca(2+) channels to interact with muscarinic M(1) receptors. The activation of these processes by vasopressin-(4-9) is critically involved in the positive effect of vasopressin-(4-9) on scopolamine-induced impairment of spatial memory.
Asunto(s)
Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Receptores de Vasopresinas/fisiología , Escopolamina/farmacología , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Acetilcolina/metabolismo , Animales , Antagonistas de los Receptores de Hormonas Antidiuréticas , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/química , Arginina Vasopresina/farmacología , Benzazepinas/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Relación Dosis-Respuesta a Droga , Hemicolinio 3/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Antagonistas de Hormonas/farmacología , Inyecciones Intraventriculares , Masculino , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/prevención & control , Inhibidores de la Captación de Neurotransmisores/farmacología , Nicardipino/farmacología , Pirenzepina/farmacología , Ratas , Ratas WistarRESUMEN
We investigated the relationship between the induction of spatial cognition impairment in the 8-arm radial maze task and regional changes (ventral hippocampus (VH), dorsal hippocampus, frontal cortex, and basolateral amygdala nucleus) in brain acetylcholine (ACh) release using microdialysis in rats treated with muscarinic (M) receptor antagonists. In a behavioral study, two M1 antagonists, scopolamine (0.5 mg/kg, i.p. and 20 microg, i.c.v.) and pirenzepine (80 microg, i.c.v.), but not an M2 antagonist, AF-DX116 (40-80 microg, i.c.v.), disrupted spatial cognition in the 8-arm radial maze task. In brain microdialysis with Ringer's solution containing 0.1 mM eserine sulfate, scopolamine and AF-DX116, but not pirenzepine, increased ACh release in the VH. Moreover, in the bilateral injection of scopolamine (2 microg/side), the VH and dorsomedial thalamus nucleus were important regions for scopolamine-induced impairment of spatial cognition. A simultaneous determination of the behavioral changes revealed that scopolamine (0.5 mg/kg, i.p.) markedly decreased the ACh contents and also increased the ACh release in all regions tested. Especially, the changes in the ACh release of the VH closely paralleled the induction of the scopolamine-induced impairment of spatial cognition. These results suggest that the blocking balance between M1 and M2 muscarinic receptor in the VH therefore plays a major role in the spatial cognition impairment induced by scopolamine in the 8-arm radial maze task.