Benzodiazepine receptor recruitment after acute stress in synaptosomal membranes from forebrain of young chicks: action of Triton X-100.
TL;DR: It is suggested that acute stress and Triton X-100 induce receptor recruitment by enhancing [3 H]-flunitrazepam accessibility to a pool of receptors which is unmeasurable either before stress or in absence of detergent.
Abstract: In young chicks submitted to acute stress by forced swimming there was a significant increase in the number of the measurable [3 H]-flunitrazepam receptors in synaptosomal membranes from forebrain. In addition, low sub-solubilizing concentrations of Triton X-100 caused a significant increase in the measurable [3H]-flunitrazepam receptor number in synaptosomal membranes from non-stressed chicks. However, this Triton X-100 stimulatory effect was not observed when tested in synaptosomal membranes from stressed chicks. In all cases the affinity remained unchanged. This result suggest that: (i) acute stress and Triton X-100 induce receptor recruitment by enhancing [3 H]-flunitrazepam accessibility to a pool of receptors which is unmeasurable either before stress or in absence of detergent; (ii) neither recruitment types are additive and they involve receptors coming from the same nonmeasurable pool; (iii) stress induces a maximal recruitment of existing benzodiazepine receptors; (iiii) the pool of nonmeasurable receptors represents about a quarter of the total in control chicks. The recruitment at a short time of stress could be interpreted in terms involving internalization; recycling or modulation of receptors but not its biosynthesis or degradation.
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TL;DR: Benzodiazepines (BZs)2 are used clinically as muscle relaxants, anticonvulsants, anxiolytics, and sedative-hypnotics.
Abstract: Benzodiazepines (BZs)2 are used clinically as muscle relaxants, anticonvulsants, anxiolytics, and sedative-hypnotics. These effects are mediated primarily via the central BZ receptors (CBRs) located in the central nervous system (CNS;[Braestrup and Squires, 1977][1]; [Mohler and Okada, 1977][2]; [
505 citations
TL;DR: For example, this paper found that acute stress induces rapid changes in GABA(A) receptors in experimental animals, with the direction of the changes varying according to the sex of the animals and the stress-paradigm studied.
Abstract: GABA(A) receptors are sensitive to subtle changes in the environment in both early-life and adulthood. These neurochemical responses to stress in adulthood are sex-dependent. Acute stress induces rapid changes in GABA(A) receptors in experimental animals, with the direction of the changes varying according to the sex of the animals and the stress-paradigm studied. These rapid alterations are of particular interest as they provide an example of fast neurotransmitter system plasticity that may be mediated by stress-induced increases in neurosteroids, perhaps via effects on phosphorylation and/or receptor trafficking. Interestingly, some studies have also provided evidence for long-lasting changes in GABA(A) receptors as a result of exposure to stressors in early-life. The short- and long-term stress sensitivity of the GABAergic system implicates GABA(A) receptors in the non-genetic etiology of psychiatric illnesses such as depression and schizophrenia in which stress may be an important factor.
63 citations
TL;DR: The results suggest that higher performance chicks were more susceptible than lower performance chicks to acute stress associated to increase of both central and peripheral type benzodiazepine receptors, probably due to differences in the degree of endogenous emotionality.
Abstract: Two-day-old chicks were selected on their second escape performance in a one-trial, maze-learning task, and termed high-performance (H-P), moderate-performance (M-P), and low-performance (L-P) chicks. The learning degree was expressed by the escape time improvement being respectively the 64, 46, and 24%. Then, the three selected groups were maintained to reach 15 days of age and then submitted to acute swimming stress, and [3H]flunitrazepam and [3H]Ro 5-4864 receptor bindings were performed on synaptosomal/mitochondrial membranes from forebrain. The receptor number for both radioligands in stressed high-performance chicks was significantly higher than in stressed low-performance chicks. The results suggest that higher performance chicks were more susceptible than lower performance chicks to acute stress associated to increase of both central and peripheral type benzodiazepine receptors, probably due to differences in the degree of endogenous emotionality.
29 citations
TL;DR: The present findings indicate that polyamines can modulate the binding characteristics of several different neurotransmitter receptor-ionophore complexes.
26 citations
TL;DR: Findings showed sexual differences in acute, stressor-induced benzodiazepine and adrenocortical responses that suggest broiler males are more stress-susceptible than females.
19 citations
References
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TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
289,852 citations
TL;DR: The number and variety of known compounrjs between proteins and small molecules are increasing rapidly and make a fascinating story as discussed by the authors, and there are many compounds of serum albumin, which was used during the war by many chemists, most of whom found at least one 6ew compound.
Abstract: The number and variety of known compounrjs between proteins and small molecules are increasing rapidly and make a fascinating story. For instance, there are the compounds of iron, which is carried in our blood plasma by a globulin, two atoms of iron to each molecule of globulin held in a rather tight salt-lie binding? which is stored as ferric hydroxide by ferritin much as water is held by a sponge? and which functions in hemoglobin, four iron atoms in tight porphyrin complexes in each protein molecule. Or, there are many compounds of serum albumin, which was used during the war by many chemists, most of whom found at least one 6ew compound. This molecule, which has about a hundred carboxyl radicals, each of which can take on a proton, and about the same number of ammonium radicals, each of which can dissociate a proton, has one single radical which combines with mercuric ion so firmly that two albumin molecules will share one mercury atom if there are not enough to go a r ~ u n d . ~ At the present stage of rapid growth of known compounds, it seems more profitable for me to make no attempt to catalogue the various classes of compounds, but to discuss the general principles involved, in the hope that this will make more useful the information which is accumulating so rapidy from so many laboratories. We want to know of each molecule or ion whicb can combine with a protein molecule, /‘How many? How tightly? Where? Why?” The answer to the first two questions, and sometimes to the third, can be furnished by the physical chemist, but he will often need to team with an organic chemist to determine the effect of altering specified groups to find if they are reactive. The determination of function iç a complicated problem which may be the business of the physiologist or physiological chemist. But the answers to both of the more complicated problems will depend on the answers to the simpler questions, “HOW many?” and “How tightly bound?” If the various groups on a protein molecule act independently, we can apply the law of mass action as though each group were on a separate molecule,4 and the strength of binding can be expressed as the constant for each group. Often, a single constant will express the behavior of severa1 groups. If the constants are widely spread, as those for the reaction of hydrogen ion with carboxylate ions, with imidazoles and with amines, the interpretation is simple. If the separation is less, it is very difficult to distinguish the case of different intrinsic affinities from the case of interaction among the groups. We know that such interaction occurs in simple moleculeç in which a reac-
20,127 citations
"Benzodiazepine receptor recruitment..." refers methods in this paper
...Figure 2 shows the Scatchard plot analysis (Scatchard, 1949) corresponding to the four experimental groups from Table 1....
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TL;DR: Amino-acid sequences derived from complementary DMAs encoding the α- and β-subunits of the GAB A/ benzo diazepine receptor from bovine brain show homology with other ligand-gated receptor subunits, suggesting that there is a super-family of ion-channel-containing receptors.
Abstract: Amino-acid sequences derived from complementary DMAs encoding the α- and β-subunits of the GAB A/ benzo diazepine receptor from bovine brain show homology with other ligand-gated receptor subunits, suggesting that there is a super-family of ion-channel-containing receptors. Co-expression of the in vitro-generated α-subunit and β-subunit RNAs in Xenopus oocytes produces a functional receptor and ion channel with the pharmacological properties characteristic of the GABAA receptor.
1,598 citations
"Benzodiazepine receptor recruitment..." refers methods in this paper
...A model for the BZD/GABAA receptor includes a site for cAMP-dependent serine phosphorylation present only in the ]3-subunit, at the intracellular side of the membrane (Schofield et al., 1987)....
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TL;DR: Data implicate 3H-diazepam binding sites in mediating at least some of the anxiolytic properties of benzodiazepines and suggest the existence of some endogenous substance which might be involved in the etiology of anxiety.
Abstract: The in vitro and in vivo ability of benzodiazepines to inhibit specific 3H-diazepam binding correlated with their ability to increase punished responding in a conflict situation. Conflict and foot shock, the punishing stimulus used in most conflict procedures, also altered 3H-diazepam binding. These data implicate 3H-diazepam binding sites in mediating at least some of the anxiolytic properties of benzodiazepines and suggest the existence of some endogenous substance which might be involved in the etiology of anxiety.
165 citations
"Benzodiazepine receptor recruitment..." refers background in this paper
...It has been reported that rat exposure to several types of stress induces changes in the number and/or the affinity of benzodiazepine (BZD) receptors from synaptosomal membranes (Lippa et al., 1978; Soubrie et al., 1980; Lane et al., 1982; Braestrup et al., 1983; Medina et al., 1983; Havoundjian et al., 1986; Trullas etal., 1987; Miller etal., 1987; R/igo etal., 1989, 1990)....
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TL;DR: The binding of [3H]Ro 5–4864, a specific ligand for “peripheral‐type” benzodiazepine binding sites and [3h]Ro 15–1788, a Specific ligands for the central benzodiazine receptors, was determined in subcellular fractions of rat brain.
Abstract: The binding of [3H]Ro 5–4864, a specific ligand for “peripheral-type” benzodiazepine binding sites and [3H]Ro 15–1788, a specific ligand for the central benzodiazepine receptors, was determined in subcellular fractions of rat brain. As previously reported, the highest levels of “peripheral-type” benzodiazepine binding sites and benzodiazepine receptors were found in the crude P1, and P2 fractions, respectively. Purification of these crude fractions revealed that high levels of both [3H]Ro 5–4864 and [3H]Ro 15–1788 binding were present in the mitochondrial and synaptosomal fractions. In contrast, the purified nuclei and myelin contained low levels of both [3H]Ro 5–4864 and [3H]Ro 15–1788 binding.
134 citations