RESUMEN
The effect of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) on the basal and stimulation-evoked release of dopamine (DA) and acetylcholine (ACh) was investigated in rat striatum. The experiments were carried out in isolated superfused striatal slices, loaded with either [3H]-dopamine or [3H]-choline. We have found that L-NAME reduced the electrical field stimulation-evoked release of DA, while its enantiomer N-nitro-D-arginine methyl ester (D-NAME) was ineffective. In the presence of the nitric oxide (NO) precursor L-arginine, L-NAME failed to influence DA release. Furthermore, treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 completely reversed the effect of L-NAME on striatal DA release. In contrast, L-NAME had no effect on either the basal or the stimulation-evoked ACh release in any experimental conditions studied. Our data indicate that endogenously produced NO is involved in the modulation of striatal DA, but not in ACh release. Furthermore, it seems likely that the modulatory effect of NO is linked to activation of presynaptic NMDA receptors located on the striatal dopaminergic nerve terminals.
Asunto(s)
Acetilcolina/metabolismo , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Óxido Nítrico/metabolismo , Animales , Arginina/análogos & derivados , Arginina/farmacología , Maleato de Dizocilpina/farmacología , Estimulación Eléctrica , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico/antagonistas & inhibidores , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/fisiologíaRESUMEN
The effect of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the response of cerebrocortical oxygen consumption (CMRO2) and blood flow (CBF) to two levels of hypercapnia (PaCO2 approximately 60 mm Hg and PaCO2 approximately 90 mm Hg) was investigated in ketamine-anesthetized rats. CBF was calculated using the Kety-Schmidt approach and CMRO2 was calculated from the product of CBF and the arteriovenous (superior sagittal sinus) difference for oxygen. L-NAME treatment did not have a significant effect on either CMRO2 or CBF under normocapnic conditions but inhibited the hypercapnic increase of CMRO2 and the hypercapnic increase in CBF. These results suggest that NO plays a role in the response of CMRO2 and CBF during hypercapnia and are consistent with the suggestion that at least part of the increase in CBF observed during hypercapnia is coupled to an increase in CMRO2.
Asunto(s)
Corteza Cerebral/metabolismo , Circulación Cerebrovascular , Hipercapnia/fisiopatología , Óxido Nítrico/fisiología , Consumo de Oxígeno , Animales , Arginina/análogos & derivados , Arginina/farmacología , Presión Sanguínea/efectos de los fármacos , Corteza Cerebral/irrigación sanguínea , Circulación Cerebrovascular/efectos de los fármacos , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico/antagonistas & inhibidores , RatasRESUMEN
In the present study the effect of selective opiate antagonists on the release of acetylcholine (ACh) and dopamine (DA) was studied in striatal slices. beta-funaltrexamine (beta-FNA) a mu receptor antagonist, naltrindole (NTI) a delta receptor antagonist and a kappa receptor antagonist nor-binaltorphimine (nor-BNI) were used to selectively block the different opioid receptor subpopulations located on the axon terminals. The receptor activation was examined on superfused slices from rat striatum previously labelled with [3H]choline or [3H]dopamine. We found that both beta-FNA and NTI significantly enhanced the evoked release of ACh using electrical field stimulation but it occurred only in those cases when dopaminergic input was impaired either by lesion of the nigrostriatal tract or by D2 dopamine receptor blocade. By contrast, under these conditions the opiate antagonists had no modulatory effect on the release of DA. Our data suggest that the release of ACh in the striatum is under the tonic control of endogenous opioid peptides. This effect is mediated via mu and delta opioid receptors. However the striatal DA release does not seem to be controlled tonically by opioid peptides.
Asunto(s)
Acetilcolina/metabolismo , Cuerpo Estriado/efectos de los fármacos , Dopamina/metabolismo , Antagonistas de Narcóticos/farmacología , Animales , Cuerpo Estriado/metabolismo , Estimulación Eléctrica , Técnicas In Vitro , Masculino , Naloxona/farmacología , Naltrexona/análogos & derivados , Naltrexona/farmacología , Oxidopamina/farmacología , Ratas , Ratas WistarRESUMEN
We investigated the effect of selective opiate antagonists on striatal acetylcholine (ACh) and dopamine (DA) release. The mu-receptor antagonist beta-funaltrexamine (beta-FNA), the delta-antagonist naltrindole (NTI), and the kappa-antagonist norbinaltorphimine (nor-BNI) were used to selectively block different subtypes of opiate receptors. The experiments were carried out on isolated superfused striatal slices of rats, loaded with [3H]choline or [3H]dopamine. beta-FNA and NTI significantly enhanced the electrical field stimulation-evoked release of ACh but only if the dopaminergic input had been impaired either by chemical denervation or D2 dopamine receptor blockade. By contrast, neither the selective nor nonselective antagonists had any modulatory effect on the release of dopamine. It is concluded, therefore, that the release of ACh is tonically controlled by endogenous opioid peptide(s) through the stimulation of mu- and delta-opiate receptors located on cholinergic axon terminals, in addition to the tonic control by DA.
Asunto(s)
Acetilcolina/metabolismo , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Antagonistas de Narcóticos/farmacología , Animales , Cuerpo Estriado/efectos de los fármacos , Indoles/farmacología , Inyecciones Intraventriculares , Masculino , Morfinanos/farmacología , Naloxona/farmacología , Naltrexona/análogos & derivados , Naltrexona/farmacología , Terminaciones Nerviosas/efectos de los fármacos , Oxidopamina , Ratas , Ratas WistarRESUMEN
We have investigated the effect of nicotinic receptor stimulation on acetylcholine (ACh) release measured by radioassay in rat striatal slices. Since the release of ACh in the striatum is tonically inhibited by endogenous dopamine and nicotine enhances the release of dopamine, we studied the release of ACh when the dopaminergic input was impaired. We used chemical denervation (6-hydroxydopamine pretreatment) or D2-receptor-blockade by sulpiride to remove the dopaminergic control of the cholinergic neurons. In our experiments nicotine failed to increase ACh release from striatal slices taken from rats whose dopaminergic-cholinergic interaction was not impaired but it enhanced the release of ACh from slices dissected from 6-hydroxydopamine pretreated rats or in the presence of sulpiride. Our results provide neurochemical evidence for the existence of nicotinic receptors on striatal cholinergic interneurons. Since the spontaneous release of ACh enhanced by nicotine was inhibited by tetrodotoxin it seems very likely that (-)-nicotine acts on the somatodendritic part of cholinergic interneurons.
Asunto(s)
Cuerpo Estriado/fisiología , Dopamina/fisiología , Nicotina/farmacología , Sistema Nervioso Parasimpático/fisiología , Acetilcolina/metabolismo , Animales , Cuerpo Estriado/citología , Cuerpo Estriado/efectos de los fármacos , Dendritas/efectos de los fármacos , Dendritas/metabolismo , Estimulación Eléctrica , Técnicas In Vitro , Interneuronas/efectos de los fármacos , Interneuronas/metabolismo , Masculino , Oxidopamina , Ratas , Ratas Endogámicas , Receptores Nicotínicos/efectos de los fármacos , Sulpirida/farmacología , Simpatectomía QuímicaRESUMEN
Naloxone significantly enhanced the release of radioactive acetylcholine ([3H]ACh) from rat striatal slices loaded with [3H]choline either when the nigrostriatal pathway had been destroyed by 6-hydroxydopamine or when the D2 dopamine receptors had been inhibited by sulpiride. This in vitro study supplies the first neurochemical evidence, that, in addition to D2-receptor-mediated dopaminergic tonic control, there is opiate-receptor mediated presynaptic modulation of striatal ACh release, possibly by endogenous enkephalin released from local neurons. Such modulation occurs under conditions in which the dopaminergic input is impaired.