There are two principal mechanisms of acetylcholine (ACh) release from the resting motor nerve terminal: quantal and non-quantal (NQR); the former being only a small fraction of the total, at least at rest. In the present article we summarize basic research about the NQR that is undoubtedly an important trophic factor during endplate development and in adult neuromuscular contacts. NQR helps to eliminate the polyneural innervation of developing muscle fibers, ensures higher excitability of the adult subsynaptic membrane by surplus polarization and protects the RMP from depolarization by regulating the NO cascade and chloride transport. It shortens the endplate potentials by promoting postsynaptic receptor desensitization when AChE is inhibited during anti-AChE poisoning. In adult synapses, it can also activate the electrogenic Na+/K+-pump, change the degree of synchronization of quanta released by the nerve stimulation and affects the contractility of skeletal muscles., F. Vyskočil, A. I. Malomouzh, E. E. Nikolsky., and Obsahuje seznam literatury
The effects of blocking ventromedial hypothalamic nucleus (VMH) muscarinic cholinoceptors on cardiovascular responses were investigated in running rats. Animals were anesthetized with pentobarbital sodium and fitted with bilateral cannulae into the VMH. After recovering from surgery, the rats were familiarized to running on a treadmill. The animals then had a polyethylene catheter implanted into the left carotid artery to measure blood pressure. Tail skin temperature (Ttail), heart rate, and systolic, diastolic and mean arterial pressure were measured after bilateral injections of 0.2 μl of 5 × 10−9 mol methylatropine or 0.15 M NaCl solution into the hypothalamus. Cholinergic blockade of the VMH reduced time to fatigue by 31% and modified the temporal profile of cardiovascular and Ttail adjustments without altering their maximal responses. Mean arterial pressure peak was achieved earlier in methylatropine-treated rats, which also showed a 2-min delay in induction of tail skin vasodilation, suggesting a higher sympathetic tonus to peripheral vessels. In conclusion, muscarinic cholinoceptors within the VMH are involved in a neuronal pathway that controls exercise-induced cardiovascular adjustments. Furthermore, blocking of cholinergic transmission increases sympathetic outflow during the initial minutes of exercise, and this higher sympathetic activity may be responsible for the decreased performance., S. P. Wanner ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The present study evaluates the protective role of Quercetin (Quer), against immobilization stress- induced anxiety, depression and cognition alteration in mice using behavioral and biochemical parameters. 24 adult Albino mice were distributed into 2 groups vehicle (n=12; 1 ml/kg) and Quer injected (n=12; 20 mg/kg/ml). The animals received their respective treatment for 14 days. On day 15, after the drug administration, animals were sub-divided into 4 groups (n=6); (i) unstressed + vehicle; (ii) stressed + vehicle; (iii) unstressed + Quer; (iv) stressed + Quer. On day 16, 24 h after the immobilization stress behavioral activities (light-dark activity, elevated plus maze, Morris water maze, and forced swim test) monitored and then animals were decapitated 1 h after the drug administration. Brain samples were collected for biochemical (antioxidant enzymes, AChE, ACh, 5-HT and its metabolite) analysis. The present study indicates the Quer reversed the stress-induced anxiety and depression, in addition, memory performance was more enhanced in stressed group. Following the treatment of Quer, stress-induced elevation of lipid peroxidation and suppression of antioxidant enzymes were also reversed. Administration of Quer decreased AChE in unstressed, while levels of acetylcholine were increased in vehicle and Quer treated stressed animals. The metabolism of 5-HT was increased in Quer treated stressed than unstressed animals. In conclusion, the present finding showed that Quer could prevent the impairment of antioxidant enzymes and also regulate the serotonergic and cholinergic neurotransmission and produce antianxiety, antidepressant effect and enhance memory following 2 h immobilization stress in mice., N. Samad, A. Saleem, F. Yasmin, M. A. Shehzad., and Obsahuje bibliografii
Fourier spectral analysis of fore arm skin laser Doppler flowmetry (LDF) signal was performed in fifteen hypercholesterolemic patients (HP), without clinically manifest arterial diseases, and in fifteen age-matched healthy control subjects (CS), in order to investigate skin blood flowmotion (SBF). The LDF frequency intervals studied were: 0.01-1.6 Hz total spectrum, as well as 0.01-0.02 Hz (endothelial), 0.02-0. 06 Hz (sympathetic), 0.06-0.2 Hz (myogenic), 0.2-0.6 Hz (respiratory) and 0.6-1.6 Hz (cardiac). Skin microvascular reactivity (MVR ) to acetylcholine (ACh) and to sodium nitroprusside (SNP) iontophoresis was also investigated. HP showed a lower post-ACh increase in power spectral density (PSD) of the 0.01-0.02 Hz SBF subinterval compared to CS (1.80±1.73 PU 2 /Hz vs 3.59±1.78 PU 2 /Hz, respectively; p<0.005), while they did not differ in MVR from CS. In eleven HP the 0.01-0.02 Hz SBF subinterval showed a higher post-ACh PSD increase near to the statistical significance after 10 weeks of rosuvastatin therapy (10 mg/day) compared to pretreatment test (3.04±2.95 PU 2 /Hz vs 1.91±1.94 PU 2 /Hz; p=0.07). The blunted post-ACh increase in PSD of the 0.01-0.02 Hz SBF subinterval in HP suggests a skin endothelial dysfunction in these patients. This SBF abnormality showed a tendency to improve after rosuvastatin therapy in eleven treated patients., M. Rossi ... [et al.]., and Obsahuje seznam literatury
We investigated the effect of pertussis toxin (PTX) on hypotensive response induced by acetylcholine (ACh) and bradykinin (BK) and on noradrenaline (NA)-induced pressor response in spontaneously hypertensive rats (SHR). Fifteen-week-old Wistar rats and age-matched SHR were used. Half of SHR received PTX (10 μg/kg/i.v.) and the experiments were performed 48 h later. After the anesthesia the right carotid artery was cannulated in order to record blood pressure (BP). The hypotensive response to ACh was enhanced in SHR compared to Wistar rats. After pretreatment of SHR with PTX the hypotensive response to ACh was reduced compared to untreated SHR and it was also diminished in comparison to Wistar rats. Similarly, the hypotensive response to BK was also decreased after PTX pretreatment. The pressor response to NA was increased in SHR compared to Wistar rats. NA-induced pressor response was considerably decreased after PTX pretreatment compared to untreated SHR. In conclusion, the enhancement of hypotensive and pressor responses in SHR was abolished after PTX pretreatment. Our results suggested that the activation of PTX-sensitive inhibitory Gi proteins is involved in the regulation of integrated vasoactive responses in SHR and PTX pretreatment could be effectively used for modification of BP regulation in this type of experimental hypertension., S. Čačányiová, F. Kristek, J. Kuneš, J. Zicha., and Obsahuje bibliografii a bibliografické odkazy
It is well known that antagonists of N-type voltage-gated calcium channels inhibit the evoked quan tal release of acetylcholine in amphibian neuromuscular synapses. This, however, does not exclude the functional expression of other types of voltage-gated calcium channels in these nerve terminals. Using immunocytochemistry, we detected the expression of the α1A subunit of P/Q-type calcium channels (that is otherwise typical of mammalian motor nerve endings) in the frog neuromuscular junction. In addition, we demonstrated that the P/Q-type channel blocker ω-agatoxin IVA (20 nM) reduced the action potential- induced calcium transient and significantly decreased both spontaneous and evoked mediator release. Our data indicates the functional expression of P/Q-type calcium channels in the frog motor nerve ending which participate in acetylcholine release., L. F. Nurullin ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy