Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The olfactory epithelium (OE) of the mouse provides a unique system for understanding how cell birth and cell death interact to regulate neuron number during development and regeneration. We have examined cell death in the OE in normal adult mice; in adult mice subjected to unilateral olfactory bulbectomy (surgical removal of one olfactory bulb, the synaptic target of olfactory receptor neurons (ORNs) of the OE); and in primary cell cultures derived from embryonic mouse OE. In vivo, cells at all stages in the neuronal lineage--proliferating neuronal precursors, immature ORNs, and mature ORNs--displayed signs of apoptotic cell death; nonneuronal cells did not. Bulbectomy dramatically increased the number of apoptotic cells in the OE on the bulbectomized side. Shortly following bulbectomy, increased cell death involved neuronal cells of all stages. Later, cell death remained persistently elevated, but this was due to increased apoptosis by mature ORNs alone. In vitro, apoptotic death of both ORNs and their precursors could be inhibited by agents that prevent apoptosis in other cells: aurintricarboxylic acid (ATA), a membrane-permeant anlog of cyclic AMP (CPT-cAMP), and certain members of the neurotrophin family of growth factors (brain-derived neurotrophic factor, neurotrophin 3, and neurotrophin 5), although no neurotrophin was as effective at promoting survival as ATA or CPT-cAMP. Consistent with observed effects of neurotrophins, immunohistochemistry localized the neurotrophin receptors trkB and trkC to fractions of ORNs scattered throughout neonatal OE. These results suggest that apoptosis may regulate neuronal number in the OE at multiple stages in the neuronal lineage and that multiple factors-potentially including certain neurotrophins--may be involved in this process.
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PMID:Apoptosis in the neuronal lineage of the mouse olfactory epithelium: regulation in vivo and in vitro. 758 10

Effects of cGMP on voltage-gated currents in the somatic membrane of isolated newt olfactory receptor cells were investigated using the whole-cell mode of the patch-clamp technique. Under voltage clamp, membrane depolarization generated time- and voltage-dependent current responses, a transient inward current and a sustained outward current. When cGMP or a membrane permeant analog of cGMP, 8-p-chlorophenylthio-cGMP (CPT-cGMP), was applied to the recorded cell, the amplitude of the transient inward current increased markedly, but that of the sustained outward current did not change significantly. When each current was isolated by pharmacological agents, 0.1 mM CPT-cGMP increased the peak amplitude of a Na(+) current (I(Na)) by approximately 40%, a T-type Ca(2+) current (I(Ca,T)) by approximately 40%, and an L-type Ca(2+)current (I(Ca,L)) by approximately 10%; however it did not change significantly the amplitude of a delayed rectifier K(+) current (I(K)). A selective cGMP-dependent protein kinase inhibitor, KT5823, blocked the enhancement by cGMP of I(Na) and I(Ca,T), suggesting that cGMP increases these currents via cGMP-dependent phosphorylation. Under current-clamp conditions, application of CPT-cGMP lowered the current threshold of action potentials induced by current injection, and increased the maximum spike frequency in response to strong stimuli. We suggest that cGMP may lower the threshold in olfactory perception by decreasing the current threshold to generate spikes, and also prevent the saturation of odor signals by increasing the maximum spike frequency.
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PMID:Modulation by cGMP of the voltage-gated currents in newt olfactory receptor cells. 1124 73

1. The suction pipette technique was used to record receptor current and spiking responses from isolated frog olfactory receptor cells during prolonged odour stimuli. 2. The majority (70 %) of cells displayed 'oscillatory' responses, consisting of repeated bursts of spikes accompanied by regular increases in receptor current. The period of this oscillation varied from 3.5 to 12 s in different cells. The remaining cells responded either with a 'transient' burst of spikes at the onset of stimulation (10 %), or by 'sustained' firing throughout the odour stimulus (20 %). 3. In cells with oscillatory responses, the Ca(2+)-activated Cl(-) channel blocker niflumic acid prolonged the period of oscillation only slightly, despite a 3.8-fold decrease in the receptor current. A 3-fold reduction in the external Cl(-) concentration nearly doubled the receptor current, but had little effect on the oscillation period. These results imply that the majority of the receptor current underlying these oscillatory responses is carried by the Ca(2+)-activated Cl(-) conductance, suggesting that the intracellular Ca(2+) concentration oscillates also. 4. In cells with oscillatory responses, the period of oscillation was prolonged 1.5-fold when stimulated in a low-Na(+) solution designed to incapacitate Na(+)-Ca(2+) exchange, irrespective of whether Na(+) was replaced by permeant Li(+) or impermeant choline. The dependence of the oscillation period upon external Na(+) suggests that it may be governed by the dynamics of Ca(2+) extrusion via Na(+)-Ca(2+) exchange. 5. Exposure to the membrane-permeable cyclic nucleotide analogue CPT-cAMP evoked a sustained rather than an oscillatory response even in cells with oscillatory responses to odour. The inability of CPT-cAMP to evoke an oscillatory response suggests that the cAMP concentration is likely to oscillate also. 6. Perforated-patch recordings revealed that oscillatory responses could only be evoked when the membrane potential was free to change, but not when it was clamped near the resting potential. Since substantial changes in Ca(2+)-activated Cl(-) current, and hence odour-induced depolarisation, had little effect upon the period of oscillation, changes in membrane potential are suggested to play only a permissive role in these oscillatory responses. 7. These results are interpreted in terms of the coupled oscillation of Ca(2+) and cyclic nucleotide concentrations within the olfactory cilia during prolonged odour stimulation.
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PMID:Responses to prolonged odour stimulation in frog olfactory receptor cells. 1143 1