scholarly journals Spinal Tolerance and Dependence: Some Observations on the Role of SpinalN-Methyl-D-Aspartate Receptors and Phosphorylation in the Loss of Opioid Analgesic Responses

2000 ◽  
Vol 5 (1) ◽  
pp. 33-39
Author(s):  
Tony L Yaksh ◽  
Xiao-Ying Hua

The continuous delivery of opiates can lead to a reduction in analgesic effects. In humans, as in other animals, some component of this change in sensitivity seems likely to have a strong pharmacodynamic component. Such loss of effect, deemed to be tolerance in the present article, can be readily demonstrated in animals with repeated bolus and continuous intrathecal infusion of mu and delta opioids and alpha-2 adrenergic agonists. Research has shown that this loss of effect can be diminished by concurrent treatment withN-methyl-D-aspartate (NMDA) receptor antagonists and by the suppression of the activity of spinal protein kinase C (PKC). This suggests in part the probable role of PKC-mediated phosphorylation in the right shift in the dose-effect curves observed with continuous opiate or adrenergic exposure. Importantly, this right shift is seen to occur in parallel with an increase in the phosphorylating activity in the dorsal horn and in the expression of several PKC isozymes. The target of this phosphorylation is not certain. Phosphorylation of the NMDA receptor enhances its functionality, while phosphorylation of the opioid receptor or associated channels seems to diminish their activity or to enhance internalization. While the focus is on several specific components, the accumulating data emphasize the biological complexity of these changes in spinal drug reactivity.

1998 ◽  
Vol 79 (6) ◽  
pp. 3266-3271 ◽  
Author(s):  
Silvarosa Grassi ◽  
Ermelinda Francescangeli ◽  
Gianfrancesco Goracci ◽  
Vito E. Pettorossi

Grassi, Silvarosa, Ermelinda Francescangeli, Gianfrancesco Goracci, and Vito E. Pettorossi. Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei. J. Neurophysiol. 79: 3266–3271, 1998. In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAFanalogue,  1 - O - hexadecyl - 2 - O - (methylcarbamyl) - sn - glycero - 3phosphocoline (MC-PAF) and the inactive PAF metabolite, 1- O-hexadecyl- sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by d,l-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-d-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.


Author(s):  
A.J. Mia ◽  
L.X. Oakford ◽  
T. Yorio

Protein kinase C (PKC) isozymes, when activated, are translocated to particulate membrane fractions for transport to the apical membrane surface in a variety of cell types. Evidence of PKC translocation was demonstrated in human megakaryoblastic leukemic cells, and in cardiac myocytes and fibroblasts, using FTTC immunofluorescent antibody labeling techniques. Recently, we reported immunogold localizations of PKC subtypes I and II in toad urinary bladder epithelia, following 60 min stimulation with Mezerein (MZ), a PKC activator, or antidiuretic hormone (ADH). Localization of isozyme subtypes I and n was carried out in separate grids using specific monoclonal antibodies with subsequent labeling with 20nm protein A-gold probes. Each PKC subtype was found to be distributed singularly and in discrete isolated patches in the cytosol as well as in the apical membrane domains. To determine if the PKC isozymes co-localized within the cell, a double immunogold labeling technique using single grids was utilized.


2013 ◽  
Author(s):  
Maisy Best ◽  
Tobias Stevens ◽  
Fraser Milton ◽  
Christopher D. Chambers ◽  
Ian P. McLaren ◽  
...  

EDIS ◽  
2013 ◽  
Vol 2013 (11) ◽  
Author(s):  
George Hochmuth ◽  
Laurie Trenholm ◽  
Don Rainey ◽  
Esen Momol ◽  
Claire Lewis ◽  
...  

Proper irrigation management is critical to conserve and protect water resources and to properly manage nutrients in the home landscape. How lawns and landscapes are irrigated directly impacts the natural environment, so landscape maintenance professionals and homeowners must adopt environmentally-friendly approaches to irrigation management. After selecting the right plant for the right place, water is the next critical factor to establish and maintain a healthy lawn and landscape. Fertilization is another important component of lawn and landscape maintenance, and irrigation must be applied correctly, especially following fertilization, to minimize potential nutrient losses. This publication supplements other UF/IFAS Extension publications that also include information on the role of soil and the root zone in irrigation management. This publication is designed to help UF/IFAS Extension county agents prepare materials to directly address nutrient losses from lawns and landscapes caused by inadequate irrigation management practices. This 6-page fact sheet was written by George Hochmuth, Laurie Trenholm, Don Rainey, Esen Momol, Claire Lewis, and Brian Niemann, and published by the UF Department of Soil and Water Science, October 2013. http://edis.ifas.ufl.edu/ss586


2020 ◽  
Vol 1 (1) ◽  
pp. 11-18
Author(s):  
M. A. Rodionov ◽  
I. V. Akimova

In the submitted study the problem of the formation of financial literacy of students at informatics lessons and relevant training of future informatics teachers is considered. Financial literacy is understood as a set of basic knowledge in the field of finance, banking, insurance, as well as budgeting for personal finances that allow a person to choose the right financial product or service, soberly assess and take risks that may arise during the use of these products, correctly accumulate savings and identify doubtful (fraudulent) investment schemes. The authors conclude that successful development of meaningful lines of the course of financial literacy requires integration of a few school subjects, such as mathematics, history, informatics, social science and literature. The role of modern informatics teacher in the formation of financial literacy of students is great. Therefore, in the training of a future informatics teacher, it should be paid the attention to issues related to the study of elements of financial literacy in informatics lessons. In order to solve the problem, the authors propose to use the special course “Basics of work in 1С:Enterprise”, which is implemented at Penza State University. The article contains a program of the course and the methodological recommendations for its implementation.


Author(s):  
Linda MEIJER-WASSENAAR ◽  
Diny VAN EST

How can a supreme audit institution (SAI) use design thinking in auditing? SAIs audit the way taxpayers’ money is collected and spent. Adding design thinking to their activities is not to be taken lightly. SAIs independently check whether public organizations have done the right things in the right way, but the organizations might not be willing to act upon a SAI’s recommendations. Can you imagine the role of design in audits? In this paper we share our experiences of some design approaches in the work of one SAI: the Netherlands Court of Audit (NCA). Design thinking needs to be adapted (Dorst, 2015a) before it can be used by SAIs such as the NCA in order to reflect their independent, autonomous status. To dive deeper into design thinking, Buchanan’s design framework (2015) and different ways of reasoning (Dorst, 2015b) are used to explore how design thinking can be adapted for audits.


2020 ◽  
Vol 8 (2) ◽  
pp. 97-108
Author(s):  
Dinda Izzati

Evidently, a few months after the Jakarta Charter was signed, Christian circles from Eastern Indonesia submitted an ultimatum, if the seven words in the Jakarta Charter were still included in the Preamble to the 1945 Constitution, then the consequence was that they would not want to join the Republic of Indonesia. The main reason put forward by Pastor Octavian was that Indonesia was seen from its georaphical interests and structure, Western Indonesia was known as the base of Islamic camouflage, while eastern Indonesia was the basis for Christian communities. Oktavianus added that Christians as an integral part of this nation need to realize that they also have the right to life, religious rights, political rights, economic rights, the same rights to the nation and state as other citizens, who in fact are mostly Muslims. This paper aims to determine and understand the extent to which the basic assumptions of the Indonesian people view the role of Islam as presented in an exclusive format.


1975 ◽  
Vol 37 (4) ◽  
pp. 532-540 ◽  
Author(s):  
Zenro IKEZAWA ◽  
Yo KAMEDA ◽  
Mitsuaki UCHIYAMA ◽  
Hiroshi NAKAJIMA ◽  
Toru BABA

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