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71.
Lucio G. Costa McNama Shao Kurt Basker Sheldon D. Murphy 《Chemico-biological interactions》1984,48(3):261-269
Male rats were treated for 10 days with the organophosphorus insecticide, acetylcholinesterase inhibitor, O,O-diethyl S-[2-(ethylthio)ethyl]phosphorodithioate (disulfoton, 2 mg/kg/day by gavage). At the end of the treatment, binding of [3H]quinuclidinyl benzilate ([3H]QNB) to cholinergic muscarinic receptors and cholinesterase (ChE) activity were assayed in the pancreas. Functional activity of pancreatic muscarinic receptor was investigated by determining carbachol-stimulated secretion of α-amylase in vitro. ChE activity and [3H]QNB binding were significantly decreased in the pancreas from disulfoton-treated rats. The alteration of [3H]QNB binding was due to a decrease in muscarinic receptor density with no change in the affinity. Basal secretion of amylase from pancreas in vitro was not altered, but carbachol-stimulated secretion was decreased. The effect appeared to be specific since pancreozymin was able to induce the same amylase release from pancreases of control and treated rats. The results suggest that repeated exposures to sublethal doses of an organophosphorus insecticide lead to a biochemical and functional alteration of cholinergic muscarinic receptors in the pancreas. 相似文献
72.
Kinetic Effects of Terbium Ions on Muscarinic Acetylcholine Receptors of Murine Neuroblastoma Cells 总被引:1,自引:1,他引:0
Esam E. El-Fakahany Michael Pfenning Elliott Richelson 《Journal of neurochemistry》1984,42(3):863-869
Preincubation of murine neuroblastoma cells (clone N1E-115) with terbium chloride resulted in a significant potentiation of carbachol-mediated increase in cyclic GMP formation. This effect was accompanied by a shift of the peak response from 30 s to 120 s and a 6-fold decrease in carbachol concentration producing half-maximal responses, in addition to a significant increase in the Hill coefficient. Terbium ions also caused a significant decrease in the affinity and an increase in the maximum binding of [3H]quinuclidinyl benzilate to muscarinic receptors, the change in affinity being mainly due to a decrease in the association rate. Preincubation of cells with 1 mM carbachol for 4 h (the desensitized state of the muscarinic receptor) resulted in a decrease in the ability of terbium to alter [3H]quinuclidinyl benzilate binding. The effects of terbium reported here might be due to its affecting muscarinic receptor-effector coupling, which is considered to be lost upon receptor desensitization. 相似文献
73.
Inositol Phospholipid Hydrolysis in Rat Cerebral Cortical Slices: I. Receptor Characterisation 总被引:35,自引:17,他引:18
Characterisation of receptor-mediated breakdown of inositol phospholipids in rat cortical slices has been performed using a direct assay which involves prelabelling with [3H]inositol. When slices were preincubated with [3H]inositol, lithium was found to greatly amplify the capacity of receptor agonists such as carbachol, noradrenaline, and 5-hydroxytryptamine to increase the amount of radioactivity appearing in the inositol phosphates. Using a large variety of agonists and antagonists it could be shown that cholinergic muscarinic, alpha 1-adrenoceptor, and histamine H1 receptors appear to be linked to inositol phospholipid breakdown in cortex. The large responses produced by receptor agonists allowed a clear discrimination between full and partial agonists as well as quantitative analysis of competitive antagonists for each receptor. Whereas carbachol and acetylcholine (in the presence of a cholinesterase inhibitor) were full agonists, oxotremorine and arecoline were only partial agonists. Very low concentrations of atropine shifted the carbachol dose-response curve to the right and allowed inhibition constants for the antagonist to be easily calculated. The nicotinic antagonist, mecamylamine, was ineffective. Noradrenaline adrenaline were full agonists at alpha 1-adrenoceptors, but phenylephrine and probably methoxamine were partial agonists. Prazosin, but not yohimbine, potently and competitively antagonised the noradrenaline inositol phospholipid response. Mepyramine but not cimetidine competitively antagonised the histamine response. These data provide strong confirmation for the potentiating effect of lithium on neurotransmitter inositol phospholipid breakdown and emphasise the ease with which functional responses at a number of cortical receptors can be characterised. 相似文献
74.
Presynaptic Nicotinic Cholinergic Receptors Labeled by [3 H]Acetylcholine on Catecholamine and Serotonin Axons in Brain 总被引:5,自引:0,他引:5
Nicotinic cholinergic receptor binding sites labeled by [3H]acetylcholine were measured in the cerebral cortices, thalami, striata, and hypothalami of rats lesioned by intraventricular injection of either 6-hydroxydopamine or 5, 7-dihydroxytryptamine. In addition, [3H]acetylcholine binding sites were measured in the cerebral cortices of rats lesioned by injection of ibotenic acid into the nucleus basalis magnocellularis. [3H]Acetylcholine binding was significantly decreased in the striata and hypothalami of both 6-hydroxydopamine- and 5,7-dihydroxytryptamine-lesioned rats. There was no change in binding in the cortex or thalamus by either lesion. Ibotenic acid lesions of the nucleus basalis magnocellularis, which projects cholinergic axons to the cortex, did not alter [3H]acetylcholine binding. These results provide evidence for a presynaptic location of nicotinic cholinergic binding sites on catecholamine and serotonin axons in the striatum and hypothalamus. 相似文献
75.
Insulin Binding in Four Regions of the Developing Rat Brain 总被引:6,自引:5,他引:1
Specific insulin binding has been demonstrated in partially purified membranes prepared from four regions of the developing rat brain. Insulin binding to brain membranes demonstrated kinetics and hormonal specificity that were quite similar to those reported for traditional insulin target tissues (e.g., liver and adipose tissue), and binding was significantly correlated with receptor concentration. Binding in the olfactory bulbs, cerebrum, cerebellum, and hypothalamus all reached highest values at 15 days of postnatal life, with the olfactory bulbs generally showing the greatest binding at all ages studied. A temporal relationship was found between insulin binding to brain membranes in the postnatal rat and plasma membrane protein synthesis, especially in the cerebellum and olfactory bulbs. 相似文献
76.
Steven P. Butcher Peter J. Roberts James F. Collins† 《Journal of neurochemistry》1984,43(4):1039-1045
Abstract: The effects of ions on the binding of the excitatory amino acid analogue dl -[3 H]2-amino-4-phosphon-obutyrate to l -glutamate-sensitive sites on rat brain synaptic membranes was investigated. The divalent cations manganese, magnesium, strontium, and particularly calcium, produced a marked enhancement in specific binding. However, this effect was manifest only in the presence of added chloride, or to a lesser extent, with bromide ions. Application of saturation analysis revealed that both chloride and calcium acted to increase the binding site density in a concentration-dependent manner, without affecting the dissociation constant. The only other ionic species found to have a significant effect on 2-amino-4-phosphonobutyrate binding was sodium, which produced an apparent reduction in site affinity, without modifying the binding site density. Although the significance of these striking ionic effects is as yet unknown, it seems feasible that chloride (and possibly also calcium) ions may serve a role in regulating the interaction of excitatory amino acids with their physiological receptors. 相似文献
77.
Richard B. Rothman Uwe K. Schumacher Candace B. Pert 《Journal of neurochemistry》1984,43(4):1197-1199
Abstract: (β-FNA, the β -fumaramate methyl ester of naltrexone, has been shown to antagonize irreversibly the actions of morphine on the guinea pig ileum and mouse vas deferens bioassays but does not affect the actions of δ-receptor ligands on the mouse vas deferens bioassay, suggesting that the compound does not irreversibly bind to the S receptor. In this paper we examine the effect of (β -FNA on the binding of the prototypic δ agonists, Leuenkephalin and d -Ala2 - d -Leu5 -enkephalin, its metabolically stable analogue, and show that treatment of membranes with β -FNA does lead to alterations in the in vitro properties of δ receptors. 相似文献
78.
pH Selectivity of N-Ethylmaleimide Reactions with Opiate Receptor Complexes in Rat Brain Membranes 总被引:1,自引:1,他引:0
N-Ethylmaleimide (NEM) decreases opiate agonist binding presumably by blocking crucial sulfhydryl (SH) groups at receptor binding sites. At physiological pH, NEM decreased GTP and manganese regulation but increased sodium effects on [3H]D-Ala2-Met5-enkephalinamide (D-Ala enk) binding to rat brain membranes. To determine the apparent pK values of putative SH groups in opiate receptors that react with NEM, rat brain membranes were incubated with 100-250 microM NEM in buffers ranging from pH 4.5 to 8.0. Results showed that lowering pH below 6.5 reduced the NEM effect on opiate receptor functions and that the apparent pK values of NEM-reacting SH groups in binding and regulatory sites ranged between 5.4 to 6.0. Most of the total SH groups in brain membranes continued to react with NEM at low pH, so that when nonspecific SH groups were blocked by incubating membranes at pH 4.5 with NEM, opiate receptors became sensitive to very low concentrations (1 microM) of NEM. 相似文献
79.
Activation of Tyrosine Hydroxylase in the Superior Cervical Ganglion by Nicotinic and Muscarinic Agonists 总被引:4,自引:3,他引:1
Both dimethylphenylpiperazinium (DMPP), a nicotinic agonist, and bethanechol, a muscarinic agonist, increase 3,4-dihydroxyphenylalanine (DOPA) synthesis in the superior cervical ganglion of the rat. DMPP causes approximately a fivefold increase in DOPA accumulation in intact ganglia whereas bethanechol causes about a two-fold increase in DOPA accumulation. These effects are additive with each other and with the increase in DOPA accumulation produced by 8-bromo cyclic AMP. The action of DMPP is dependent on extracellular Ca2+ while the actions of bethanechol and 8-bromo cyclic AMP are not dependent on extracellular Ca2+. Cholinergic agonists and cyclic nucleotides produce a stable activation of tyrosine hydroxylase (TH) in the ganglion. The activation of TH by nicotinic and muscarinic agonists can be detected after 5 min of incubation of the ganglia with these agents. The nicotinic response disappears after 30 min of incubation, whereas the muscarinic response persists for at least 30 min. The Ca2+ dependence of the TH activation produced by these agents is similar to the Ca2+ dependence of their effects on DOPA accumulation in intact ganglia. These data are consistent with the hypothesis that nicotinic agonists, muscarinic agonists, and cyclic AMP analogues increase TH activity by three distinct mechanisms. The activation of TH presumably underlies the increase in DOPA synthesis produced by these agents. 相似文献
80.
Gabriella Fóris MD PhD George A. Medgyesi Mátyás Hauck 《Molecular and cellular biochemistry》1986,69(2):127-137
Summary Met-enkephalin (ME) exerts a bimodal effect on functional activities of rat peritoneal macrophages (PM); in a range of low concentration (10-9-10-7 M) antibody dependent cellular cytotoxicity (ADCC)was markedly stimulated with a simultaneous decrease of Fc receptor (FcR) mediated phagocytosis while the opposite was observed at 10-6-10-5 M concentrations.Studying the possible underlying mechanism(s) the followings were recorded: (1) ME in all applied concentrations induced an early Na+ influx which was followed by a Ca2+ efflux in the range of low concentrations. In the range of high concentrations Na+ influx was accompanied by a Ca2+ influx. (2) ME at 10-8 M concentration induced a rise in cGMP level with a plateau in the 60–120th min of incubation. This effect was prevented by 10-5 M of naloxone. At 10-6 M concentration a transient rise of cAMP level was recorded which was not affected by naloxone. (3) Verapamil in 10-6 M abolished both the Ca2+ influx and the rise in cAMP level induced by 10-6-10-5 M ME but not the rise in cGMP level induced by lower ME concentrations. (4) cAMP elevation by high ME concentrations was abolished by enkephalinase inhibitory puromycin. (5) PM-enkephalinase as assessed by the cleavage of fluorogenic substrate L-alanine beta naphthylamide (ABNA), was inhibited by 10-6-10-5 M of ME. This inhibition was abolished by verapamil, but not affected by naloxone. In the range of low concentrations ME appears to act on specific delta opioid receptors and its action is positively coupled to guanylate cyclase. In relatively higher concentrations ME-action is not mediated by specific delta opioid receptors and it appears to involve Ca2+ influx, adenylate cyclase activation as well as the processing of hormone by PM-enkephalinase. 相似文献