Neurotoxicity of Olindias sambaquiensis and Chiropsalmus quadrumanus extracts in sympathetic nervous system

Cnidarians are equipped with nematocysts, which are specialized organelles used to inoculate venom during prey capturing and defense. Their venoms are rich in toxins and a potential source of bioactive compounds, however, poorly explored so far. In this work, the activity of the methanolic extracts from the hydromedusa Olindias sambaquiensis and the cubozoan jellyfish Chiropsalmus quadrumanus were studied in sympathetic neurotransmission. For that, bisected rat vas deferens - a classic model of sympathetic neurotransmission - were incubated with the extracts for further myographic and histopathological analysis. The O. sambaquiensis extract, at 0.1 μg/mL, facilitated the neurogenic contractions of the noradrenergic-rich epididymal portion, while reducing the noradrenaline (NA) potency, which suggests an interaction with postsynaptic α1-adrenoceptors. On the other hand, a higher concentration (1 μg/mL) leads to time- and frequency-dependent blockade of nerve-evoked contractions without significantly changing the response to exogenous NA. In turn, the C. quadrumanus extract at 0.1 μg/mL induced blockade of nerve-evoked noradrenergic contractions while reducing the potency to exogenous NA. Both extracts did not affect the purinergic neurotransmission or induce muscle damages. Our results demonstrate that O. sambaquiensis and C. quadrumanus extracts significantly interfere with the noradrenergic neurotransmission without altering purinergic response or smooth muscle structure on rat vas deferens. Such results bring to light the pharmacological potential of O. sambaquiensis and C. quadrumanus molecules for therapeutics focusing on noradrenergic neurotransmission.

Effects of in vitro, acute and chronic treatment with fluoxetine on the sympathetic neurotransmission of rat vas deferens.

It is described that fluoxetine treatment is able to induce ejaculatory disorders. However, the exact mechanism is still not fully understood. Therefore, this study was carried out to further evaluate the anti-ejaculatory effects of fluoxetine, using different approaches (in vitro or in vivo treatments), on the sympathetic neurotransmission of the rat vas deferens. Vas deferens from male Wistar rats were used to check the in vitro effects of fluoxetine 10-6M, 3.10-6M or 10-5M. Animals were also acutely (20mg/kg, i.p. 4h or 24h) or chronically (10mg/kg, i.p., 30days) treated with fluoxetine or drug-free vehicle. The vas deferens from non-treated and treated animals were isolated and mounted in an isolated organ bath for the study of the contractions induced by adrenergic agonists, tyramine, 5-HT, Ca2+ or electrical field stimulation. In vitro or acute treatment with fluoxetine decreased the contraction induced by agonists, Ca2+ or electrical field stimulation. The chronic treatment with fluoxetine decreased the contractions induced agonists, tyramine or Ca2+, but did not modify the contractions induced by electrical field stimulation. We have shown that in vitro or in vivo fluoxetine treatment is able to alter the sympathetic neurotransmission of the rat vas deferens which could be related to alterations in the calcium signalling.

Relationship between central behavioral effects and peripheral sympathetic neurotransmission functionality during acute cocaine withdrawal syndrome in adult rats.

BACKGROUND: Acute cocaine withdrawal syndrome (ACWS) is characterized as a set of organic alterations triggered by abrupt discontinuation of chronic cocaine consumption, usually occurring at 24-40 hours after withdrawal. However, little is known about the relationship between central and peripheral sympathetic neurotransmission during ACWS. OBJECTIVE AND METHODS: We investigated the mechanisms involved in central and peripheral sympathetic neurotransmission and how ACWS affects the sympathetic functionality. Cocaine was administered twice daily for 5 days in Wistar rats (at least 5 in each group): on the first and second day, 15 mg/kg/i.p.; third day, 20 mg/kg/i.p.; and finally in the last two days, 30 mg/kg/i.p. Subsequently, at 1, 24, 48 and 120 h after cocaine administration the following experiments were done: (i) at the central level, behavioral tests of open-field and elevated plus maze; and (ii) at the peripheral level, tests of catecholamine release, function of α2-adrenergic receptors (α2-ARs), imidazoline receptors (I(1,2)-Rs), L-type voltage-gated (Ca(v1.2)) Ca(2+) channels and α1-ARs. RESULTS: During ACWS, rats showed hypolocomotion and exacerbation of anxiogenic-effects 24 h after cocaine withdrawal. Likewise, a decrease in the catecholamine release and activity of α2-ARs/I(1,2)-Rs at 24-48 h after cocaine withdrawal was observed. A decrease in Ca(v1.2) channels and α1-ARs function at 48 h after cocaine withdrawal was observed. CONCLUSIONS: The relationship of central and peripheral sympathetic neurotransmission during ACWS possibly due to a failure in activation and/or inactivation of presynaptic α2-ARs/I(1,2)-Rs, may offer a potential target for attenuating ACWS.

Chronic treatment with red wine modulates the purinergic neurotransmission and decreases blood pressure in hypertensive SHR and diabetic-STZ rats.

It is known that red wine has cardioprotective properties. However, its influence is unknown about purinergic system. Therefore, we study the influence of the treatment with red wine or ethanol in purinergic neurotransmission. We used Wistar Kyoto rats (WKY), diabetic streptozotocin-induced WKY and spontaneously hypertensive rats (SHR), treated with red wine (12.5%) or ethanol (12.5%). The cardiovascular function stimulated with purinergic agonists and systolic blood pressure (SBP) was assessed. In atria of diabetics and SHRs, the P1 receptor response was decreased, unlike the P2 receptor response was increased. Likewise, in aorta the affinity to adenosine (ADO) was decreased from SHRs and diabetics. Furthermore, the P2X function was increased just SHRs. All these alterations were improved after treatment with red wine, resulting in reduction of SBP from diabetics and SHRs, but not when treated with ethanol. This study has important implications, because it is shown that consumption of red wine can improve cardiovascular system by purinergic neurotransmission.

Influence of acute treatment with sibutramine on the sympathetic neurotransmission of the young rat vas deferens.

The effects of acute treatment with sibutramine on the peripheral sympathetic neurotransmission in vas deferens of young rats were still not evaluated. Therefore, we carried out this study in order to verify the effects of acute sibutramine treatment on the neuronal- and exogenous agonist-induced contractions of the young rat vas deferens. Young 45-day-old male Wistar rats were pretreated with sibutramine 6 mg/kg and after 4h the vas deferens was used for experiment. The acute treatment with sibutramine was able to increase the potency (pD2) of noradrenaline and phenylephrine. Moreover, the efficacy (Emax) of noradrenaline was increased while the efficacy of serotonin and nicotine were decreased. The maximum effect induced by a single concentration of tyramine was diminished in the vas deferens from treated group. Moreover, the leftward shift of the noradrenaline curves promoted by uptake blockers (cocaine and corticosterone) and ß-adrenoceptor antagonist (propranolol) was reduced in the vas deferens of treated group. The initial phasic and secondary tonic components of the neuronal-evoked contractions of vas deferens from treated group at the frequencies of 2 Hz were decreased. Moreover, only the initial phasic component at 5 Hz was diminished by the acute treatment with sibutramine. In conclusion, we showed that the acute treatment with sibutramine in young rats was able to affect the peripheral sympathetic nervous system by inhibition of noradrenaline uptake and reduction of the neuronal content of this neurotransmitter, leading to an enhancement of vas deferens sensitivity to noradrenaline.