Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.69 (botulinum neurotoxin)
 1,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of L-aspartate as a classical neurotransmitter of the CNS has been a matter of great debate. In this study, we have characterized the main mechanisms of its depolarization-induced release from rat purified cerebrocortical synaptosomes in superfusion and compared them with those of the well known excitatory neurotransmitter L-glutamate. High KCl and 4-aminopyridine were used as depolarizing agents. At 15 mM KCl, the overflows of both transmitters were almost completely dependent on external Ca2+. At 35 and 50 mM KCl, the overflows of L-aspartate, but not those of L-glutamate, became sensitive to DL-threo-b-benzyloxy aspartic acid (DL-TBOA), an excitatory amino acid transporter inhibitor. In the presence of DL-TBOA, the 50 mM KCl-evoked release of L-aspartate was still largely external Ca2+-dependent. The DL-TBOA insensitive,external Ca2+-independent component of the 50 mM KCl-evoked overflows of L-aspartate and L-glutamate was significantly decreased by the mitochondrial Na+/Ca2+ exchanger blocker CGP 37157. The Ca2+-dependent, KCl-evoked overflows of L-aspartate and L-glutamate were diminished by botulinum neurotoxin C, although to a significantly different extent. The 4-aminopyridine-induced L-aspartate and L-glutamate release was completely external Ca2+-dependent and never affected by DL-TBOA. Superimposable results have been obtained by pre-labeling synaptosomes with [3H]D aspartate and [3H]L-glutamate. Therefore, our data showing that L-aspartate is released from nerve terminals by calcium dependent,exocytotic mechanisms support the neurotransmitter role of this amino acid.
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PMID:L-aspartate as an amino acid neurotransmitter: mechanisms of the depolarization-induced release from cerebrocortical synaptosomes. 1954 7

The afferent innervation of the urinary bladder consists primarily of small myelinated (Adelta) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract.
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PMID:Afferent nerve regulation of bladder function in health and disease. 1965 6