Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392674 (exhaustion)
 13,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diamide, which in concentrations of 10(-5) M and higher oxidizes glutathione intracellularly, produces a dose-related increase in the frequency of miniature end-plate potentials (MEPPs). With high enough doses, quantal release is blocked, apparently through exhaustion. The early phase of MEPP frequency increase is accompanied by an increase in EPP amplitude that may reach more than 10-fold and is therefore not produced by depolarization of axon terminals. Subsequently, EPP amplitude is reduced and falls to zero, associated with failure of invasion of the nerve action into the terminals while the MEPP frequency remains elevated. Both facilitation and PTP follow the time course of change in EPP amplitude. The increase in MEPP frequency with diamide does not require external Ca2+ but raising external Ca2+ increases the MEPP rate in the presence of diamide. External Ca2+ is necessary for EPP appearance and also potentiates the diamide effects. Conversely diamide reduces the requirements for Ca2+ in releasing ACh. Diamide substitutes for external Ca2+ in K+ evoked MEPP release and in the absence of external Ca2+, diamide-evoked MEPP release is increased by raising external Mg2+ levels. The action of diamide may be dependent on the actual release of Ca2+ from intracellular stores or it may work through mimicking some of the actions of Ca2+. The action of diamide bears close resemblance to the effects of prolonged stimulation of the motor axon at 10 Hz.
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PMID:The thiol-oxidizing agent diamide increases transmitter release by decreasing calcium requirements for neuromuscular transmission in the frog. 18 54

The effects of acute exercise on receptor-mediated endothelium-dependent vasodilation and its possible mechanisms were investigated in the presence of indomethacin. Male Wistar rats (16-20 weeks old) were divided into control and exercise groups. The exercise group ran on a drum exerciser until exhaustion, followed by immediate decapitation. Acetylcholine (ACh)- or clonidine (CLO)-induced vasodilating responses in thoracic aortae of the control and exercise groups were compared. Receptor-binding assays were performed to determine whether there were any upregulations of endothelial receptors after acute exercise. Our results indicated that acute exercise induced the following effects: (1) the dose-response curves of ACh and CLO shifted to the left; (2) the high-affinity M3 binding sites increased in number but not in affinity; (3) the alpha2 binding sites decreased in number but increased in affinity. We conclude that acute exercise enhances receptor-mediated vasodilation responses, at least in part, by regulating either endothelial receptor number or receptor affinity.
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PMID:Acute exercise enhances receptor-mediated endothelium-dependent vasodilation by receptor upregulation. 993 39

The role of endothelial calcium signaling in exercise-enhanced ACh-induced vasorelaxation was examined using male Wistar rats (8~10 wk old) that were divided into control and exercise groups. The exercised animals ran on a treadmill with progressive increments of speed until exhaustion. After decapitation, aortic rings were dissected and loaded with fura 2-AM. After being mounted on a tissue flow chamber, vessels were precontracted with phenylephrine, and ACh-induced endothelial calcium elevation and vasorelaxation were determined simultaneously under an epifluorescence microscope equipped with ratio imaging capability. Our results showed that 1) there was logarithmic correlation between endothelial calcium elevation and vasorelaxation; 2) acute exercise enhanced ACh-induced endothelial calcium elevation and vasorelaxation without altering their relationship; 3) pretreatment with N(omega)-nitro-L-arginine markedly reduced ACh-induced vasorelaxation in both groups but suppressed the calcium response only in the exercise group; and 4) the exercise effect on endothelial calcium elevation was abolished by Ca2+-free buffer or gadolinium. In conclusion, acute exercise increases ACh-induced vasorelaxation by increasing the endothelial calcium influx and the calcium-dependent nitric oxide release.
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PMID:Acute exercise enhances vasorelaxation by modulating endothelial calcium signaling in rat aortas. 1183 95

NO is known to reduce the hypoxia-induced increase in carotid body neural activity (CBNA). Acetylcholine (ACh), a known excitatory transmitter in the cat carotid body (CB), is released during hypoxia. This study addressed the impact of an NO precursor on ACh release during hypoxia. Both CBs from nine cats were prepared for incubation, then inserted into a medium and bubbled with three consecutive gas mixtures, hyperoxic, hypoxic, and a final hyperoxic mixture. This series of exposures was performed in the absence of L-arginine, followed by the three exposures in a 1mM L-arginine medium, and followed, thirdly, in a 10mM L-arginine medium. L-Arginine significantly attenuated the hypoxia-induced release of ACh. Two post-arginine procedures suggested strongly that the reduction in the ACh release was not due to a gradual exhaustion of carotid body ACh stores over the course of the experiment. The data are consistent with those reports showing that NO donors and precursors reduce the hypoxia-induced increase in CBNA, and further support a role for ACh in the hypoxia-induced increase in CBNA.
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PMID:L-arginine's effect on the hypoxia-induced release of acetylcholine from the in vitro cat carotid body. 1584 19

Acetylcholine (ACh) has not been tested for a role in the development of sexual exhaustion in males. However, male hamsters receiving infusions into the medial preoptic area (MPOA) of the muscarinic agonist oxotremorine (OXO) or antagonist scopolamine (SCO) show changes in the postejaculatory interval, one of the measures that changes most consistently as exhaustion approaches. In addition, central SCO treatments cause changes in the patterning of intromissions that resemble those signaling exhaustion. To extend these observations and more thoroughly test the dependence of sexual exhaustion on ACh, male hamsters received MPOA treatments of OXO, SCO or the combination of the two before mating to exhaustion. Relative to placebo, OXO infusions caused small but consistent increases in ejaculation frequency and long intromission latency, delaying the appearance of exhaustion. Scopolamine treatments did the reverse, dramatically accelerating the development of exhaustion. Consistent with and possibly responsible for these changes were effects on the quality of performance prior to exhaustion. These included differences in overall copulatory efficiency (e.g., ejaculations/intromission), which was increased by OXO and decreased by SCO. They also extended to several standard measures of copulatory behavior, including intromission frequency, ejaculation latency and the postejaculatory interval: Most of these were increased by SCO and decreased by OXO. Finally, whereas most or all effects of OXO were counteracted by SCO, most or all of the responses to SCO resisted change by added OXO. This asymmetry in the responses to combined treatment raises the possibility that the effects of these drugs on sexual exhaustion and other elements of male behavior are mediated by distinct muscarinic receptors.
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PMID:Oxotremorine delays and scopolamine accelerates sexual exhaustion when applied to the preoptic area in male hamsters. 2379 38