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

In AtT20 mouse corticotroph tumour cells large conductance Ca2+-activated K+-channels (BK-channels) have an essential role in the early glucocorticoid inhibition of adrenocorticotrophin (ACTH) secretion evoked by corticotrophin-releasing factor. The present study examined whether or not BK-channels are also pivotal to glucocorticoid inhibition of normal rat anterior pituitary cells. A membrane-permeant, non-metabolizable cyclic AMP analogue, 8-(4-Chlorophenylthio)adenosine-3',5'-cyclic-monophosphate (CPT-cAMP) was used as the primary secretagogue stimulus, as this mimics the increase of intracellular cyclic AMP caused by corticotrophin-releasing factor, but is not subject to the complex Ca2+-dependent regulation of cyclic AMP metabolism that is evident in corticotroph cells. Experiments in AtT20 cells showed that ACTH secretion stimulated by 1 mM CPT-cAMP was suppressed to 34+/-1.5% (n = 12) of the control stimulus by a maximal dose of 100 nM dexamethasone. The ACTH secretion evoked by the combination of 1 mM CPT-cAMP with either 5 microm (-)BayK8644 (L-type Ca2+-channel activator) or 5 mM TEA (K+-channel blocker) was respectively 69.1+/-7.6% and 69.3+/-11.8% of control after 2 h preincubation with 100 nM dexamethasone (P<0.05 vs CPT-cAMP). The ACTH response elicited by 5 microM (-)BayK8644 and 5 mM TEA given together was completely resistant to inhibition by 100 nM dexamethasone. Furthermore, TEA and (-)BayK8644 given together synergistically stimulated ACTH release in combination with 0.1 mM or 1 mM CPT-cAMP, and these ACTH responses were not inhibited by 100 nM dexamethasone. In primary cultures of rat anterior pituitary cells, TEA (up to 20 mM), charybdotoxin (30 nM) or apamin (100 nM) failed to modify the glucocorticoid inhibition of 0.1 mM CPT-cAMP-induced ACTH release. The combination of 5 mM TEA and 5 microM (-)BayK8644 elicited a small but significant increase in ACTH secretion but did not modify the inhibition of 0.3 mM CPT-cAMP-induced ACTH secretion by 100 nM dexamethasone. In primary cultures of rat anterior pituitary cells, depolarization of the membrane potential with 40 mM KCl enhanced the ACTH response to CPT-cAMP and markedly reduced the maximal inhibitory effect of dexamethasone to 55+/-1.2% as well as that of corticosterone to 33+/-2.1% vs 100+/-2.5% and 100+/-1.9% inhibition respectively, when 0.1 mM CPT-cAMP was used alone. Introduction of 5 microM (-)BayK8644 with 40 mM KCl in this system had no additional effect on glucocorticoid inhibition. No glucocorticoid inhibition of ACTH release to any of the stimuli applied was observed in cells pretreated with the mRNA synthesis inhibitor, 5,6-dichloro-furanosyl-benzimidazole riboside (DRB) (0.1 mM) or the protein synthesis blocker, puromycin (0.1 mM). In summary, early glucocorticoid inhibition of stimulated ACTH release by cultured rat anterior pituitary cells was dependent on the synthesis of new mRNA and protein. Depolarization of the membrane potential potentiated CPT-cAMP-induced ACTH secretion in AtT20 cells as well as cultured rat corticotrophs and this was associated with a resistance to the early inhibitory effect of glucocorticoids. Glucocorticoid inhibition in rat anterior pituitary corticotrophs was unaltered by TEA, charybdotoxin as well as apamin, and hence it is unlikely to involve predominantly BK-or SK-type Ca2+-activated K+-channels. These results support the thesis that a prime target of glucocorticoid feedback inhibition in anterior pituitary corticotrophs is the membrane potential and indicate that glucocorticoid-induced proteins regulate the activities of several distinct plasma membrane ion channels.
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PMID:Depolarization counteracts glucocorticoid inhibition of adenohypophysical corticotroph cells. 975 91

The role of adenosine in reversible inhibition of synaptic function during the early stage of anoxia and its mechanisms were investigated with extracellular recording technique in rat hippocampal slices. The results showed that acute anoxia led to the reversible inhibition of synaptic function, which is similar to the response to addition of high concentration of exogenous adenosine. The reversible inhibition could be suppressed by adenosine A1 receptor antagonist CPT and potassium channel blocker 4-AP, whereas TEA and ATP-sensitive potassium channel blocker glipzide had no effect. These results suggest that during the early stage of anoxia, the enhanced release of endogenous adenosine can inhibit the synaptic transmission by activating 4-AP-sensitive potassium channels via A1 receptors and thus play a role in protenction against anoxic injury. ATP-sensitive potassium channels may not be involved in the mechanisms of adenosine action.
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PMID:[The role of adenosine in the early stage of anoxia of hippocampal slices and its mechanisms]. 1007 22

The properties of the hyperpolarization-activated inward cation current (Ih) in mouse anterior pituitary, AtT20 D16:16 corticotropes was characterized by whole cell patch clamp recording. In response to hyperpolarizing steps a large, slowly activating, voltage-dependent inward current was activated with a half maximal activation voltage (V0.5) of -96.2+/-3.1 mV with a time constant of 168+/-13 msec determined at -140 mV at room temperature. Ih had a reversal potential of -35.5+/-1.0 mV and -23.3+/-1.4 mV using 5 mM and 25 mM extracellular K+, respectively, with a relative permeability ratio for Na+ and K+ of 0.24. The current was completely blocked by 2 mM extracellular CsCl and partially blocked by ZD7288 (100 microM) but was unaffected by TEA (10 mM) or Ba2+ (1 mM). RT-PCR analysis revealed robust expression of HCN1, but not HCN2 or HCN3, subunits of hyperpolarization-activated cation channels. The endogenous Ih current was weakly activated by cAMP but robustly inhibited by the cAMP antagonist, Rp-8-CPT-cAMPS. Activation or suppression of protein kinase C activity had no significant effect on the Ih current. The data suggest that in AtT20 D16:16 corticotropes Ih is tonically regulated by the cAMP-signaling cascade and may serve to limit excessive hyperpolarization.
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PMID:Characterization of hyperpolarization-activated cation currents in mouse anterior pituitary, AtT20 D16:16 corticotropes. 1091 81