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mAChR Subtypes (machr + subtype)
Selected AbstractsInhibition of ,7-containing nicotinic ACh receptors by muscarinic M1 ACh receptors in rat hippocampal CA1 interneurones in slicesTHE JOURNAL OF PHYSIOLOGY, Issue 5 2009Jian-xin Shen Cys-loop ligand-gated nicotinic ACh receptors (nAChRs) and G protein-coupled muscarinic ACh receptors (mAChRs) are expressed on rat hippocampal interneurones where they can regulate excitability, synaptic communication and cognitive function. Even though both nAChRs and mAChRs appear to co-localize to the same interneurones, it is not clear whether there is crosstalk between them. We utilized patch-clamp techniques to investigate this issue in rat hippocampal CA1 interneurones in slices under conditions where synaptic transmission was blocked. The ,7 nAChR-mediated currents were activated by choline, and when the activation of this receptor was preceded by the activation of the M1 mAChR subtype, the amplitude of ,7 responses was significantly reduced in a rapidly reversible and voltage-independent manner, without any change in the kinetics of responses. This M1 mAChR-mediated inhibition of ,7 nAChRs was through a PLC-, calcium- and PKC-dependent signal transduction cascade. These data show that M1 mAChRs and ,7 nAChRs are functionally co-localized on individual rat hippocampal interneurones where the activation of these particular mAChRs inhibits ,7 nAChR function. This information will help to understand how these cholinergic receptor systems might be regulating neuronal excitability in the hippocampus in a manner that has relevance for synaptic plasticity and cognition. [source] The M5 muscarinic receptor as possible target for treatment of drug abuseJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2009R. B. Raffa Summary Two reports published in the latter 1980s are generally given credit for being the first to announce the discovery of a new subtype of muscarinic acetylcholine receptor (mAChR), designated m5 or M5, and now officially M5 (1). Both identifications were assigned using molecular biology techniques. Then , as now , no selective high-affinity ligands or toxins were available. In situ hybridization and reverse-transcriptase PCR have found M5 AChR expression in brain to be distinct from that of the four other G protein-coupled mAChR subtypes and primarily localized to the substantia nigra, ventral tegmental area, hippocampus (CA1 and CA2 subfields), cerebral cortex (outermost layer) and striatum (caudate putamen). M5 AChR brain region localization and involvement in the regulation of striatal dopamine release and in rewarding brain stimulation suggests a possible role for M5 AChR as a target for novel therapy to treat excess hedonic drive, including drug abuse. [source] Role of M2, M3, and M4 muscarinic receptor subtypes in the spinal cholinergic control of nociception revealed using siRNA in ratsJOURNAL OF NEUROCHEMISTRY, Issue 4 2009You-Qing Cai Abstract Muscarinic acetylcholine receptors (mAChRs) are involved in the control of nociception in the spinal cord. The M2, M3, and M4 mAChR subtypes are present in the spinal dorsal horn. However, the role of the individual subtypes in the anti-nociceptive effect produced by mAChR agonists is uncertain. Here, we determined the contribution of M2, M3, and M4 subtypes to spinal muscarinic analgesia by using small-interference RNA (siRNA) targeting specific mAChR subtypes in rats. The neuronal uptake and distribution of a chitosan-siRNA conjugated fluorescent dye in the spinal cord and dorsal root ganglion were confirmed after intrathecal injection. The control and gene-specific siRNA-chitosan complexes were injected intrathecally for three consecutive days. Quantitative reverse-transcription polymerase chain reaction analysis showed that treatment with siRNA targeting M2, M3, or M4 subtype produced a large reduction in the corresponding mRNA levels in the dorsal root ganglion and dorsal spinal cord. Also, the protein levels of the mAChR subtypes in the spinal cord were significantly down-regulated by siRNA treatment, as determined by the immunoprecipitation and receptor-binding assay. Treatment with the M2 -siRNA caused a large reduction in the inhibitory effect of muscarine on the nociceptive withdrawal threshold. Furthermore, M4 knockdown at the spinal level significantly reduced the anti-nociceptive effect of muscarine. However, the anti-nociceptive effect of muscarine was not significantly changed by the M3 -specific siRNA. Our study suggests that chitosan nanoparticles can be used for efficient delivery of siRNA into the neuronal tissues in vivo. Our findings also provide important functional evidence that M2 and M4, but not M3, contribute to nociceptive regulation by mAChRs at the spinal level. [source] | ||||||||||