No description available.

published_or_final_version / Physiology / Master / Master of Medical Sciences

Glutamate is the most abundant excitatory neurotransmitter in the mammalian nervous system. Ionotropic glutamate receptors used to be the only type of glutamate receptors, bringing about essential functions including synaptic transmissions. Since 1991, eight metabotropic glutamate receptors have been discovered. Belonging to the subfamily C of G protein-coupled receptor (GPCR) superfamily, these receptors have unique structural features. They couple to their own specific G proteins and transduce signals via pathways not recognized in other subfamilies. To date, little information on these receptors have been revealed in mammals, and even less is known about them in non-mammalian species including chicken. In the present study, various cDNAs of the chicken glutamate receptor, metabotropic 1 (GRM1) as well as its splice variants were cloned from adult brain tissue. At least 11 exons were identified in the chicken (c-) GRM1 gene, in which the alternative usage of exons and splice acceptor sites results in at least three variants, namely cGRM1a, cGRM1b and cGRM1f. The predicted coding regions of cGRM1a, cGRM1b and cGRM1f are 3459 base pairs (bp), 2736 bp and 2697 bp in length, which were deduced to encode receptor peptides of 1152 amino acids (aa), 911 aa and 898 aa, respectively. The predicted cGRM1a peptide shows high amino acid sequence identities (87.5% to 88%) to its counterparts in humans, rats, mice, chimpanzees and cattle. cGRM1b transcript differs from cGRM1a transcript by inclusion of two additional exons (7b and 7c), which contains a premature stop codon and results in its shorter C-terminal tail. cGRM1f is a novel splice variant that lacks exon 7b and is 13 aa shorter than cGRM1b. Reverse transcription-polymerase chain reaction (RT-PCR) assays showed that the transcripts of cGRM1a, cGRM1b and cGRM1f were preferentially expressed in adult chicken brains, in which cGRM1f mRNA was additionally identified in pituitary, lungs and gonads. Functional assay demonstrated that cGRM1a and cGRM1b receptors, expressed in Chinese hamster ovary cells, were induced by glutamate in dose-dependent manners via the Fura-2 dye calcium assays. In addition, dual luciferase reporter assays suggested that cGRM1a and cGRM1b receptors have no significant effects on the activation of cAMP/PKA and MAPK/ERK signaling pathways upon glutamate treatment. Taken together, the present study has provided the first step in understanding the possible roles of GRM1 in chickens. / published_or_final_version / Biological Sciences / Master / Master of Philosophy

No description available.

Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains xviii, 160 p.; also includes graphics Includes bibliographical references (p. 132-160). Available online via OhioLINK's ETD Center

Thesis (Ph. D.)--University of Hong Kong, 2005.

The indirect in vivo inhibition of the enzyme glutamic acid decarboxylase (GAD) by either vitamin B-6 deficiency or the administration of vitamin B-6 antimetabolites decreases the conversion of glutamic acid to gamma aminobutyric acid (GABA) in brain. This decrease is a concomitant to the occurrence of seizures resembling grand mal. The in vivo reactivation of GAD by vitamin B-6 administration and/or by the topical application of GABA to the brain surface reduces the intensity of the convulsions. Because of this, it has been suggested that a decrease in the conversion of glutamic acid to GABA in brain may be a factor in the precipitation and maintenance of epileptic seizures. In order to investigate this suggestion, the in vivo metabolism of C-14 labelled glutamic acid to GABA and other amino acids was quantitatively determined in various brain areas of several normal cats; a cat with a epileptogenic lesion in the left motor cortex produced by alumina cream; and one cat in status epilepticus. Throughout most non-epileptogenic brain areas there were similar rates of conversion of glutamic acid to GABA, aspartic acid and glutamine. Notable exceptions to this consistency were found repeatedly in the quadri-geminal plate, thalamus and putamen-globus pallidus where there was a higher conversion of glutamic acid to GABA. No apparent consistency in the degree of conversion of glutamic acid to the other amino acids could be discerned throughout the brain of the cat in status epilepticus. In the epileptogenic lesion there was a decrease in the conversion of glutamic acid to GABA, which is compatible with the suggestion that a reduction in GABA levels increases the degree of brain excitability. / Medicine, Faculty of / Graduate

The system involved in mechanotransduction by proprioceptive sensory organs, such as muscle spindles, is poorly understood. We previously reported that stretch releases glutamate from synaptic-like vesicles (SLVs) within muscle spindle terminals (the proprioceptive sensory organs of muscles), and activates a non-canonical mGluR, modulating afferent firing (Bewick et al, 2005). If, as our previous data and the literature suggests, this system is present in other mechanosensory endings, such as baroreceptors, it presents a drugable target in the treatment of hypertension. With current hypertension therapy ineffective in around 20% of patients a novel target such as this is highly important to investigate. This study aimed to further investigate this receptor's pharmacology by screening ligands selective for classical mGluRs for their ability to alter stretch-evoked spindle firing in muscle spindles and SLV uptake in lanceolate endings. I found that although there are differences between the two systems, overall the pharmacology most closely matches that of the currently unsequenced phospholipase D coupled mGluR previously studied in the hippocampus (Pellegrini-Giampietro et al., 1996). Furthermore the pharmacology does not match that of any canonical mGluR (or iGluR). This pharmacological profiling allowed the development of novel kainate-derived compounds which were tested to find more potent analogues suitable for “click chemistry” (Kolb et al, 2001). The development of these compounds allowed further compounds to be synthesised with biotin and fluorescent side chains which will be used in further studies ultimately to allow sequencing of the receptor. In respect to baroreceptors I expanded our data in the working-heart-brainstem model and developed an isolated aortic preparation which will be used in further studies to further characterise this SLV/glutamate system in baroreceptors.

Univ., Diss.--Göteborg, 2006. / Enth. außerdem 5 Zeitschriftenaufsätze.

Thesis (Ph.D.)--Tufts University, 1975. / Submitted to the Dept. of Chemistry. Access restricted to members of the Tufts University community. Also available via the World Wide Web;