Effects of elevated pressures of inert gases on cytosolic free Ca2+ of cultured human neuroblastoma cells stimulated with carbachol: relevance to high pressure neurological syndrome
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The carbachol-mediated inhibition of cAMP synthesis in membranes of rat cerebral cortex revealed maximum in 0.3 mM carbachol solution, while further increases of the drug concentration blocked the inhibitory effect and restored the adenylate cyclase activity. The bell-shaped dose-response curve was analyzed assuming that carbachol binds with two distinct sites on muscarinic receptor, which are responsible for agonistic and antagonistic effects, related to this receptor. The pKagon and pKant values for carbachol were 5.0 and 2.1, respectively.
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cyclic monophosphate (cyclic GMP) concentrations may increase electrical stability of the myocardium was examined by determination of ventricular fibrillation thresholds (VFT) on isolated perfused hearts of the rat. Hearts were paced to circumvent any complicating effects of bradycardia. Using this system, carbachol produced a concentration‐related reduction in VFT. The reduction in VFT produced by carbachol was not significantly modified by a high concentration of atenolol (10 −5 M), indicating that the increased vulnerability to ventricular fibrillation was not an indirect consequence of catecholamine release from intramyocardial stores. Atropine (10 −6 M) blocked the carbachol‐induced reduction in VFT. At the concentrations of carbachol used to reduce VFT, myocardial cyclic GMP concentrations were also elevated. The dibutyryl analogue of cyclic GMP (10 −4 M) mimicked the effect of carbachol in reducing VFT. Carbachol potentiated the adrenaline (3 × 10 −7 M)‐induced reduction in VFT.
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Carbachol, a muscarinic receptor agonist, produced three distinct spontaneous oscillations in the CA3 region of rat hippocampal slices. Carbachol concentrations in the 4-13 microM range produced regular synchronized CA3 discharges at 0.5-2 Hz (carbachol-delta). Higher concentrations (13-60 microM) produced short episodes of 5-10 Hz (carbachol-theta) oscillations separated by nonsynchronous activity. Concentrations of carbachol ranging from 8-25 microM also produced irregular episodes of high-frequency discharges (carbachol-gamma, 35-70 Hz), in isolation or mixed with carbachol-theta and carbachol-delta. At carbachol concentrations sufficient to induce carbachol-theta, low concentrations of APV reversibly transformed carbachol-theta into carbachol-delta. Higher concentrations of D,L-2-amino-5-phosphonopentanoic acid (APV) reversibly and completely blocked carbachol-theta. A systematic study of the effects of carbachol shows that the frequency of spontaneous oscillations depended nonlinearly on the level of muscarinic activation. Field and intracellular recordings from CA1 and CA3 pyramidal cells and interneurons during carbachol-induced rhythms revealed that the hippocampal circuitry preserved in the slice was capable of spontaneous activity over the range of frequencies observed in vivo and suggests that the presence of these rhythms could be under neuromodulatory control.
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Abstract: Mouse N1E‐115 neuroblastoma cells were used to study carbachol induced changes in muscarinic cholinergic parameters. Cells were treated with carbachol (1 mM) for up to 96 hours. The number of muscarinic receptors, measured in 3 H‐3‐quinuclidinyl benzilate binding experiments, decreased approximately 50% after 4 hours exposure to carbachol. This was followed by an increase in binding sites, and after 24 hours the number of binding sites was the same as in control cells. The changes observed in the choline esterase activity followed the same pattern. The increase in number of binding sites was not dependent on protein synthesis, while the increase in choline esterase activity was. The muscarinic receptor‐stimulated uptake of 45 Ca2 + showed an initial decrease, which was followed by a significantly increased basal uptake of 45 Ca 2+ . It is suggested that all these changes are adaptations of long time exposure to carbachol.
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Carbachol, a muscarinic receptor agonist, produced three distinct spontaneous oscillations in the CA3 region of rat hippocampal slices. Carbachol concentrations in the 4–13 μM range produced regular synchronized CA3 discharges at 0.5–2 Hz (carbachol-delta). Higher concentrations (13–60 μM) produced short episodes of 5–10 Hz (carbachol-theta) oscillations separated by nonsynchronous activity. Concentrations of carbachol ranging from 8–25 μM also produced irregular episodes of high-frequency discharges (carbachol-gamma, 35–70 Hz), in isolation or mixed with carbachol-theta and carbachol-delta. At carbachol concentrations sufficient to induce carbachol-theta, low concentrations of APV reversibly transformed carbachol-theta into carbachol-delta. Higher concentrations of D,L-2-amino-5-phosphonopentanoic acid (APV) reversibly and completely blocked carbachol-theta. A systematic study of the effects of carbachol shows that the frequency of spontaneous oscillations depended nonlinearly on the level of muscarinic activation. Field and intracellular recordings from CA1 and CA3 pyramidal cells and interneurons during carbachol-induced rhythms revealed that the hippocampal circuitry preserved in the slice was capable of spontaneous activity over the range of frequencies observed in vivo and suggests that the presence of these rhythms could be under neuromodulatory control. Hippocampus 10:187–197, 2000 © 2000 Wiley-Liss, Inc.
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