RESUMO

In this study, we hypothesized that blunting of the natriuresis response to intracerebroventricularly (i.c.v.) microinjected cholinergic and adrenergic agonists is involved in the development of hypertension in spontaneously hypertensive rats (SHR). We evaluated the effect of i.c.v. injection of cholinergic and noradrenergic agonists, at increasing concentrations, and of muscarinic cholinergic and α1 and α2-adrenoceptor antagonists on blood pressure and urinary sodium handling in SHR, compared with age-matched Wistar Kyoto rats (WR). We confirmed that CCh and NE microinjected into the lateral ventricle (LV) of conscious rats leads to enhanced natriuresis. This response was associated with increased proximal and post-proximal sodium excretion accompanied by an unchanged rate of glomerular filtration. We showed that cholinergic-induced natriuresis in WR and SHR was attenuated by previous i.c.v. administration of atropine and was significantly lower in the hypertensive strain than in WR. In both groups the natriuretic effect of injection of noradrenaline into the LV was abolished by previous local injection of an α1-adrenoceptor antagonist (prazosin). Conversely, LV α2-adrenoceptor antagonist (yohimbine) administration potentiated the action of noradrenaline. The LV yohimbine pretreatment normalized urinary sodium excretion in SHR compared with age-matched WR. In conclusion, these are, as far as we are aware, the first results showing the importance of interaction of central cholinergic and/or noradrenergic receptors in the pathogenesis of spontaneous hypertension. These experiments also provide good evidence of the existence of a central adrenergic mechanism consisting of α1 and α2-adrenoceptors which works antagonistically on regulation of renal sodium excretion.

Assuntos

RESUMO

Melatonin, the darkness hormone, synchronizes several physiological functions to light/dark cycle. Besides the awake/sleep cycle that is intuitively linked to day/night, daily variations in memory acquisition and innate or acquired immune responses are some of the major activities linked to melatonin rhythm. The daily variation of these complex processes is due to changes in specific mechanisms. In the last years we focused on the influence of melatonin on the expression and function of nicotinic acetylcholine receptors (nAChRs). Melatonin, either "in vivo" or "in vitro", increases, in a selective manner, the efficiency of alpha-bungarotoxin (alpha-BTX)-sensitive nAChRs. Melatonin's effect on receptors located in rat sympathetic nerve terminals, cerebellum, skeletal muscle and chick retina, was tested. We observed that melatonin is essential for the development of alpha-BTX-sensitive nAChRs, and important for receptor maintenance in aging models. Taking into account that both melatonin and alpha-7 nAChRs (one of the subtypes sensitive to alpha-BTX) are involved in the development of Alzheimer's disease, here we discuss the possibility of a therapeutic strategy focused on both melatonin replacement and its potential association with cholinergic drugs.

Assuntos

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus ilicifolia Mart. ex. Reissek (Celastraceae) is widely used in Brazilian folk medicine to treat gastric disturbances. AIM OF THE STUDY: This work intended to characterize the effects of Maytenus ilicifolia on gastrointestinal motility. MATERIALS AND METHODS: Gastric emptying and intestinal transit were measured in the same animal. Mice received a semisolid marked with phenol red, half an hour after treatment with extracts. The amount of marker in the stomach and the distance reached in the intestine after 15 min were measured as index of gastrointestinal emptying and intestinal transit, respectively. RESULTS: Intraperitoneal administration of a flavonoid-rich extract potently reduced the gastric emptying (ED(50)=89 mg/kg) and the intestinal transit (ED(50)=31 mg/kg) of mice. Bio-guided purification of the flavonoid-rich extract by chemical partition with solvents of decreasing polarity yielded fraction insF with about 12-14 times higher activity than the initial flavonoid extract in both the gastric emptying and the intestinal transit. The inhibitory effects of the insF (9.7 mg/kg, i.p.) on gastric emptying and intestinal transit were reversed by co-administration of bethanechol (10 mg/kg, s.c.) but not by co-administration of metoclopramide (30 mg/kg, p.o.) indicating muscarinic but not dopaminergic interaction of the compounds of Maytenus. Chemical investigation of the insF fraction by HPLC-MS allowed the identification of 4 free flavonoids (catechin, epicatechin, quercetin and kaempferol), 29 flavonol glycosides and 8 tannins. The flavonol glycosides ranged from 1 to 4 monosaccharide units, having mainly quercetin and kaempferol as aglycone moieties, and the tannins were composed by catechin/epicatechin and/or afzelechin/epiafzelechin. CONCLUSIONS: Overall, the results indicate that the components of Maytenus ilicifolia have a potential use in the treatment of gastrointestinal motility disturbances such as diarrhea.

Assuntos

RESUMO

CF-1 male mice were trained in an inhibitory avoidance task using a high footshock (1,2 mA, 50 Hz, 1 sec) in order to reduce the influence of extinction on retention performance. At 2, 7, 14, or 30 d after training, the first retention test was performed and hemicholinium (HC-3, 1.0 microg/mice), a specific inhibitor of high-affinity choline uptake in brain cholinergic neurons, was given intracerebroventricularly immediately after. Twenty four hours after treatment, mice were tested in an inhibitory avoidance task during five consecutive days, each 24 h apart. Retention performance was impaired by HC-3 when the first re-exposure took place at 2, 7, or 14 d, but the effect was no longer seen when re-exposure occurred 30 d after training. We did not find spontaneous recovery 21 d after training, when memory was retrieved 2 d after training and HC-3 was given immediately after. Although we cannot definitively discard a retrieval deficit, this lack of spontaneous recovery is in accordance with the storage-deficit interpretation. These results confirm and extend previous ones, suggesting that central cholinergic mechanisms are involved in the hypothetical reconsolidation memory processes of an inhibitory avoidance task in mice and also suggest that this participation depends on the "age" of the original memory trace. This implies that the vulnerability of a reactivated memory to a specific treatment, as the one used in this study, inversely correlates with the age of the original memory, and it is likely to determine memory reconsolidation processes.

Assuntos

RESUMO

The immediate post-training i.c.v. administration of hemicholinium-3 (HC-3) (1 microg), a specific inhibitor of the high-affinity choline uptake (HACU) in brain cholinergic neurons, impaired retention test performance of a one-trial step-through inhibitory avoidance response in adult male CF-1 mice. The effect was observed in mice that received a footshock (0.8 mA, 50 Hz, 1 s) on the learning trial, and not only 48 h after training, but also 7 days after it. After the completion of the retention test at each of the training-test interval that were studied, the HACU in the hippocampus of HC-3-treated mice was not significantly different from that of saline-injected (1 microl) control groups. Mice that were over-reinforced (1.2 mA, 50 Hz, 1 s) on the learning trial, exhibited a high retention performance 48 h after training. The immediate i.c.v. injection of HC-3 (1 microg) after the retention test, that is, after memory reactivation, significantly impaired retention performance over 4 consecutive days, whereas the saline-injected control group shown a slight, but significant performance decrease only at the last retention test. Retention performance was unchanged in HC-3-treated mice not undergoing memory reactivation session. These results, taken together, indicate that HC-3, not only impaired consolidation, but also reconsolidation of an inhibitory avoidance task in mice, suggesting a critical participation of central cholinergic mechanisms in both memory processes.

Assuntos

RESUMO

Trigeminal neuralgia and cluster headache syndrome are complex pain conditions of the craniofacial region. Both diseases can coexist in the same patient, comprising the cluster-tic syndrome. This article reviews the literature on this condition and reports a new case who responded well to peripheral streptomycin-lidocaine injections.

Assuntos

Assuntos