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)

In the preceding paper (Kehoe, 1985) it was shown that the firing of any one of three neurones (I, II, III) presynaptic to the medial cells of the pleural ganglion of Aplysia californica causes a diminution of the cholinergically controlled K conductance in those cells. Firing of the same three presynaptic neurones was shown here to cause a similar diminution in a depolarization-induced K-dependent conductance in the same post-synaptic cells. The depolarization-induced K conductance was found to disappear when Ca ions were removed from the sea water bathing the ganglion or when the cell was injected with the Ca chelator ethyleneglycol-bis-(beta-aminoethylether)N,N'-tetra-acetic acid (EGTA). The diminution in this Ca-activated, K-dependent current occurred even when the presynaptic neurone was fired a few seconds after the end of the depolarizing voltage step to the post-synaptic neurone, showing that the diminution in K conductance was not an indirect effect of a transmitter-induced diminution in Ca influx during the depolarizing pulse. The two K conductances affected by the 'blocking neurones' could be selectively eliminated. The cholinergic conductance could be blocked by receptor-specific cholinergic antagonists (e.g. 1 mM concentrations of phenyltrimethylammonium (PTMA), choline and tetraethylammonium (TEA]. Even at 10 mM concentrations, none of these compounds (including TEA, which is known to block certain Ca-activated K conductances) had an effect on the depolarization-induced, Ca-activated K conductance studied here. This latter conductance, on the other hand, was selectively blocked by an intracellular injection of EGTA. The three blocking neurones continued to diminish the K conductance (cholinergic or depolarization induced) that remained intact under these different experimental conditions. The depolarization-induced influx of Ca was shown to block the cholinergically controlled K conductance, but Ca was excluded as the possible mediator of the diminution in K conductance caused by the three blocking neurones. An intracellular injection of Ca ions into the medial cells was shown to activate a variety of changes in membrane conductance; in particular, two K-conductance increases: an early, TEA-sensitive one, and a slowly developing, TEA-insensitive one. Both the permeant cyclic AMP analogue p-chlorophenylthioadenosine 3',5'-monophosphate (CPT-cyclic AMP) and the phosphodiesterase inhibitors amino-phylline and isobutyl-1-methylxanthine (IBMX) were shown to block the depolarization-induced K conductance, and to reduce, though not eliminate, the slowly developing K conductance activated by an intracellular injection of Ca.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Synaptic block of a calcium-activated potassium conductance in Aplysia neurones. 241 50

Protein phosphorylation plays important roles in the mechanisms underlying serotonin (5-HT)-induced presynaptic facilitation of Aplysia sensory neurons. To study mechanisms involved in facilitation, we investigated the pattern of protein phosphorylation in sensory neurons as a function of different durations of 5-HT. Two minutes and 1.5 hr treatments with 5-HT altered the phosphorylation of 5 and 10 proteins, respectively. These different duration treatments with 5-HT produced unique effects on the phosphorylation of different sets of proteins. This result suggests that cells may encode and measure the duration of a stimulus by the pattern of specific proteins that are phosphorylated or dephosphorylated. In addition, because the changes in phosphorylation produced by 2 min treatments with 5-HT were not observed after 25 min treatments with 5-HT, mechanisms must exist for the transient phosphorylation of some proteins even when the 5-HT treatment persists. Anisomycin, an inhibitor of protein synthesis, blocked the effect of 1.5 hr treatments with 5-HT on the phosphorylation of six proteins but had no effect on the phosphorylation change of four other proteins. Both CPT-cAMP (an activator of protein kinase A) and PDAc (an activator of protein kinase C) mimicked the effects of 5-HT on four proteins. Interestingly, the effect of 5-HT on these four proteins did not require protein synthesis. CPT-cAMP, but not PDAc, mimicked the effect of 5-HT on one protein (L55) and, the effect of 5-HT on this protein appeared to require protein synthesis. Because both activation of PKA and protein synthesis are involved in the induction of long-term facilitation, protein L55 is a good candidate for a protein that might play a key role in long-term facilitation. Finally, the effects of 5-HT on four proteins were not mimicked by either CPT-cAMP or PDAc. This finding raises the interesting possibility that some effects of 5-HT are mediated by second-messenger systems other than PKA or PKC.
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PMID:Dynamics of protein phosphorylation in sensory neurons of Aplysia. 782 47

Nociceptive sensory neurons (SNs) in Aplysia provide useful models to study both memory and adaptive responses to nerve injury. Induction of long-term memory in many species, including Aplysia, is thought to depend on activation of cAMP-dependent protein kinase (PKA). Because Aplysia SNs display similar alterations in models of memory and after nerve injury, a plausible hypothesis is that axotomy triggers memory-like modifications by activating PKA in damaged axons. The present study disproves this hypothesis. SN axotomy was produced by (1) dissociation of somata from the ganglion [which is shown to induce long-term hyperexcitability (LTH)], (2) transection of neurites of dissociated SNs growing in vitro, or (3) peripheral nerve crush. Application of the competitive PKA inhibitor Rp-8-CPT-cAMPS at the time of axotomy failed to alter the induction of LTH by each form of axotomy, although the inhibitor antagonized hyperexcitability produced by 5-HT application. Strong activation of PKA in the nerve by coapplication of a membrane-permeant analog of cAMP and a phosphodiesterase inhibitor was not sufficient to induce LTH of either the SN somata or axons. Furthermore, nerve crush failed to activate axonal PKA or stimulate its retrograde transport. Therefore, PKA activation plays little if any role in the induction of LTH by axotomy. However, the expression of LTH was reduced by intracellular injection of the highly specific PKA inhibitor PKI several days after nerve crush. This suggests that long-lasting activation of PKA in or near the soma contributes to the maintenance of long-term modifications produced by nerve injury.
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PMID:Activation of protein kinase A contributes to the expression but not the induction of long-term hyperexcitability caused by axotomy of Aplysia sensory neurons. 995 2