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Receptor Involvement (receptor + involvement)
Selected AbstractsPeripheral sensitization in migraine,role for P2X purinergic receptors in the dura,vascular sensory pathwayDRUG DEVELOPMENT RESEARCH, Issue 6 2007Ernest A. Jennings Abstract Peripheral sensitization is still considered a prime contributor underlying the mechanisms of migraine. Trigeminal primary afferent neurons are the first neurons in the dural nociceptive pathway, and activation results in conscious perception of pain. Peripheral sensitization can lower the activation threshold of primary afferent neurons, rendering them more excitable, allowing for increases in release of neurotransmitter from both central and peripheral terminals. Increase in neurotransmitter release from central terminals contributes to excitation of second-order neurons, while the release of peptides from peripheral terminals has been implicated in neurogenic inflammation. Adenosine 5,-triphosphate (ATP) causes pain in human studies, and depolarize sensory neurons. There is evidence of the action of ATP at many levels in the dura,vascular sensory pathway. Animal studies have shown that some P2X receptors are located in neurons innervating the dura, including the P2X3 receptor, which is most often shown to be involved in nociceptive pathways. In this article, we briefly review peripheral sensitization in relation to migraine and provide emphasis for P2X receptor involvement where it is available. Drug Dev Res 68:321,328, 2007. © 2007 Wiley-Liss, Inc. [source] Reduced aggression in AMPA-type glutamate receptor GluR-A subunit-deficient miceGENES, BRAIN AND BEHAVIOR, Issue 5 2004O. Y. Vekovischeva The importance of AMPA-type glutamate receptors has been demonstrated in neuronal plasticity and in adaptation to drugs of abuse. We studied the involvement of AMPA receptors in social interaction and anxiety and found that in several paradigms of agonistic behavior naïve male mice deficient for the GluR-A subunit- containing AMPA receptors are less aggressive than wild-type littermates. GluR-A deficient mice and wild-type littermates exhibited similar basic behavior and reflexes as monitored by observational Irwin's test, but they tended to be less anxious in elevated plus-maze and light-dark tests. Maternal aggression or male-female encounters were not affected which suggests that male hormones are involved in the expression of suppressed aggressiveness. However, testosterone levels and brain monoamines can be excluded and found to be similar between GluR-A deficient and wild-type littermates. The reduced AMPA receptor levels caused by the lack of the GluR-A subunit, and measured by a 30% reduction in hippocampal [3H]-S-AMPA binding, seem to be the reason for suppressed male aggressiveness. When we analyzed mice with reduced number of functional AMPA receptors mediated by the genomic introduced GluR-A(Q582R) channel mutation, we observed again male-specific suppressed aggression, providing additional evidence for GluR-A subunit-containing AMPA receptor involvement in aggression. [source] Differential involvement of the dorsal hippocampus in passive avoidance in C57bl/6J and DBA/2J miceHIPPOCAMPUS, Issue 1 2008Petra J.J. Baarendse Abstract The inferior performance of DBA/2 mice when compared to C57BL/6 mice in hippocampus-dependent behavioral tasks including contextual fear conditioning has been attributed to impaired hippocampal function. However, DBA/2J mice have been reported to perform similarly or even better than C57BL/6J mice in the passive avoidance (PA) task that most likely also depends on hippocampal function. The apparent discrepancy in PA versus fear conditioning performance in these two strains of mice was investigated using an automated PA system. The aim was to determine whether these two mouse strains utilize different strategies involving a different contribution of hippocampal mechanisms to encode PA. C57BL/6J mice exhibited significantly longer retention latencies than DBA/2J mice when tested 24 h after training irrespective of the circadian cycle. Dorsohippocampal NMDA receptor inhibition by local injection of the selective antagonist DL -2-amino-5-phosphonovaleric acid (AP5, 3.2 ,g/mouse) before training resulted in impaired PA retention in C57BL/6J but not in DBA/2J mice. Furthermore, nonreinforced pre-exposure to the PA system before training caused a latent inhibition-like reduction of retention latencies in C57BL/6J, whereas it improved PA retention in DBA/2J mice. These pre-exposure experiments facilitated the discrimination of hippocampal involvement without local pharmacological intervention. The results indicate differences in PA learning between these two strains based on a different NMDA receptor involvement in the dorsal hippocampus in this emotional learning task. We hypothesize that mouse strains can differ in their PA learning performance based on their relative ability to form associations on the basis of unisensory versus multisensory contextual/spatial cues that involve hippocampal processing. © 2007 Wiley-Liss, Inc. [source] TRPV1 in colitis: is it a good or a bad receptor?NEUROGASTROENTEROLOGY & MOTILITY, Issue 8 2007a viewpoint Abstract, The role of the transient receptor potential vanilloid-1 (TRPV1) receptor has been repeatedly investigated in animal models of inflammation. The present issue of Neurogastroenterology and Motility includes another report on this issue and not unexpectedly, many questions on the precise role of TRPV1 receptors in inflammation remain unanswered. This Editorial Viewpoint discusses the present knowledge on TRPV1 receptor involvement in intestinal inflammation and discusses the question whether the TRPV1 has to be regarded as the good or the bad receptor in this context. Since TRPV1 activation turns out being a valuable approach, translation of this knowledge to human disease is highly recommended. [source] Normalization of A2A and A3 adenosine receptor up-regulation in rheumatoid arthritis patients by treatment with anti,tumor necrosis factor , but not methotrexateARTHRITIS & RHEUMATISM, Issue 10 2009Katia Varani Objective To investigate A1, A2A, A2B, and A3 adenosine receptors in lymphocytes and neutrophils from patients with early rheumatoid arthritis (ERA) as well as from RA patients treated with methotrexate (MTX) or anti,tumor necrosis factor , (anti-TNF,), as compared with those in age-matched healthy controls, and to examine correlations between the status and functionality of adenosine receptors and TNF, release and NF-,B activation. Methods Adenosine receptors were analyzed by saturation binding assays and Western blot analyses. We investigated the potency of typical A2A and A3 agonists in the production of cAMP in control subjects, ERA patients, and RA patients treated with MTX or anti-TNF,. In a separate cohort of RA patients, TNF, release and NF-,B activation were evaluated in plasma and nuclear extracts, respectively. Results In ERA patients, we found a high density and altered functionality of A2A and A3 receptors. The binding and functional parameters of A2A and A3 receptors normalized after anti-TNF,, but not MTX, treatment. TNF, release was increased in ERA patients and in MTX-treated RA patients, whereas in anti-TNF,,treated RA patients, release was comparable to that in the controls. NF-,B activation was elevated in ERA patients and in MTX-treated RA patients. Anti-TNF, treatment mediated decreased levels of NF-,B activation. Conclusion A2A and A3 receptor up-regulation in ERA patients and in MTX-treated RA patients was associated with high levels of TNF, and NF-,B activation. Treatment with anti-TNF, normalized A2A and A3 receptor expression and functionality. This new evidence of A2A and A3 receptor involvement opens the possibility of exploiting their potential role in human diseases characterized by a marked inflammatory component. [source] |