RESUMEN
The antinociceptive effect of purine nucleotides administered systematically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P1 (caffeine, 5, 10, of 30 mg/kg); theophylline, 10 mg/kg) or purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that antinociceptive effect of adenine nucleotides is mediated by adenosine.
Asunto(s)
Nociceptores/efectos de los fármacos , Nucleótidos de Purina/farmacología , Analgésicos/farmacología , Animales , Cafeína/farmacología , Masculino , Ratones , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Quinidina/farmacología , Receptores Purinérgicos P1/efectos de los fármacos , Receptores Purinérgicos P2/efectos de los fármacos , Colorantes de Rosanilina/farmacología , Suramina/farmacología , Teofilina/farmacologíaRESUMEN
The antinociceptive effect of purine nucleotides administered systemically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P1 (caffeine, 5, 10 or 30 mg/kg); theophylline, 10 mg/kg) or purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that the antinociceptive effect of adenine nucleotides is mediated by adenosine.
Asunto(s)
Ratones , Animales , Masculino , Analgésicos/farmacología , Cafeína/farmacología , Inflamación/tratamiento farmacológico , Naloxona/farmacología , Quinidina/farmacología , Colorantes de Rosanilina/farmacología , Suramina/farmacología , Teofilina/farmacología , Receptores Purinérgicos P1/efectos de los fármacos , Receptores Purinérgicos P2/efectos de los fármacosRESUMEN
Previous studies have demonstrated that post-training intrahippocampal glutamate administration improves inhibitory avoidance task performance in rats. Antagonism of the agonist actions of glutamate by guanine nucleotides has been shown at the molecular and behavioural level. In the present investigation we demonstrate that intrahippocampal co-administration of GMP (guanosine 5'-monophosphate) reverses the facilitatory effect of glutamate on the inhibitory avoidance learning paradigm and inhibits [3H]glutamate binding in hippocampal synaptic plasma membranes. These results suggest that guanine nucleotides may modulate glutamate actions.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Ácido Glutámico/farmacología , Guanosina Monofosfato/farmacología , Hipocampo/fisiología , Neuronas/fisiología , Análisis de Varianza , Animales , Relación Dosis-Respuesta a Droga , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Masculino , Neuronas/efectos de los fármacos , Ratas , Ratas Wistar , Membranas Sinápticas/efectos de los fármacos , Membranas Sinápticas/metabolismoRESUMEN
The effect of intrastriatal administration of methylmalonic acid (MMA), a metabolite that accumulates in methylmalonic aciduria, on behavior of adult male Wistar rats was investigated. After cannula placing, rats received unilateral intrastriatal injections of MMA (buffered to pH 7.4 with NaOH) or NaCl. MMA induced rotational behavior toward the contralateral side of injection and clonic convulsions in a dose-dependent manner. Rotational behavior and convulsions were prevented by intrastriatal preadministration of MK-801 and attenuated by preadministration of succinate. This study provides evidence for a participation of NMDA receptors in the MMA-induced behavioral alterations, where succinate dehydrogenase inhibition seems to have a pivotal role.