Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein phosphorylation and dephosphorylation play an important role in neuronal signal transduction. In this study the distribution of calcineurin, a calcium/calmodulin-dependent protein phosphatase, was investigated in the striate cortex of two Old World monkeys, Macaca fascicularis and Papio anubis, using a well-characterized, affinity-purified polyclonal antibody to calcineurin. In order to relate the calcineurin distributions to established cytochemical markers, adjacent sections were processed for the visualization of cytochrome oxidase. The staining patterns obtained from the two species were remarkably similar. The results indicate that (1) monkey striate cortex exhibits strong calcineurin-like immunoreactivity that is present both in the neuropil and in neurons, most of which have characteristics of pyramidal cells; (2) the distribution of calcineurin is laminar specific; and (3) it is complementary to that of cytochrome oxidase activity with respect to both its laminar and its tangential pattern. In sections perpendicular to the cortical lamination calcineurin immunoreactivity is high in layers II and III, reduced in layer IVA, nearly as dense as in supragranular layers in layer IVB, minimal in layer IVC, and again enhanced, but not as much as in supragranular layers, in layers V and VI. In addition to these lamina-specific variations, the density of calcineurin-like immunoreactivity exhibits a periodic modulation along trajectories parallel to the pial surface that is most marked in layer III but also discernable in infragranular layers. Accordingly, in tangential sections through supragranular layers the calcineurin distribution is mosaic-like with patches of high density corresponding to cytochrome-poor regions (interblob regions) and zones of low density corresponding to areas of high cytochrome oxidase activity (blobs).
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PMID:Laminar and columnar organization of immunoreactivity for calcineurin, a calcium- and calmodulin-regulated protein phosphatase, in monkey striate cortex. 770 89

1. Nicotine stimulated two Ca(2+)-dependent processes in rat frontal cortex synaptosomes: the phosphorylation of an 80-kDa protein band and the release of endogenous ACh.3 Both effects were mediated by neuronal nAChRs and coincided with depolarization of the synaptosomal plasma membrane induced by the drug. Changes in the state of phosphorylation of the 80-kDa band (presumed to contain synapsin I) were correlated with changes in the release of ACh as follows, from 2 to 4. 2. Blockade of predominant, nerve terminal P-type Ca2+ channels with omega-agatoxin-IVA, did not prevent nicotine from stimulating ACh release. In contrast, exposure to the toxin partially inhibited the release promoted by the depolarizing agent veratridine and attenuated protein phosphorylation induced by either nicotine or veratridine. Taken together, these data suggest that, upon nicotine stimulation. Ca2+ enters nerve terminals through two distinct pathways. The first, via Ca2+ channels, is necessary (but not sufficient) for both nicotine-induced phosphorylation and ACh release. The second, both necessary and sufficient for nicotine-induced phosphorylation and release, is the neuronal nAChR itself. 3. Preincubation of the synaptosomes with a subeffective concentration of nicotine inactivated both nicotine-induced ACh liberation and phosphorylation. This shows that diminished release is associated to decreased phosphorylation of the 80-kDa protein band, most likely as a consequence of nicotine-promoted nAChR desensitization. 4. Augmented ACh release and phosphorylation of the 80-kDa protein band were achieved by using the protein phosphatase inhibitor okadaic acid. However, okadaic acid did not summate with either nicotine or veratridine to increase ACh release further. This is probably because okadaic acid, as in other neurons, increases intracellular Ca2+ (Cholewinski et al., 1993), thus promoting desensitization of ACh release.
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PMID:Concomitant protein phosphorylation and endogenous acetylcholine release induced by nicotine: dependency on neuronal nicotinic receptors and desensitization. 778 41

Previously, we have presented evidence for the presence of L-type voltage-dependent Ca2+ channels (VDCC) in 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, (acetoxymethyl)ester (BAPTA-AM)-incubated motor nerve terminals (MNTs) of the levator auris muscle of mature mice. The aim of the present work was to study the coupling of these L-type VDCC to neurotransmitter release by inhibiting protein phosphatases. We thus studied the effects of the protein phosphatase inhibitors okadaic acid (OA) and pervanadate on quantal content (QC) of transmitter release with the P/Q-type channels fully blocked. The QC was not significantly different under the three experimental conditions tested: incubation with dimethylsulphoxide (DMSO), ethylene-glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid, (acetoxymethyl)ester (EGTA-AM) and BAPTA-AM. After preincubation with OA (1 microM), but not with pervanadate, QC increased substantially in the BAPTA-AM-incubated (up to 400%) MNT, but not in those incubated with DMSO or EGTA-AM. The OA-induced increment of QC was attenuated greatly (approximately 95% reduction) by preincubation with either nitrendipine (10 microM) or calciseptine (300 nM). The effect of OA (1 microM) and pervanadate (0.1 mM) on spontaneous neurotransmitter release was also studied. After preincubation with OA, but not per-vanadate, miniature end-plate potential (MEPP) frequency increased only in the BAPTA-AM-incubated MNT (up to 700% increment). This response was attenuated (by approximately 80%) by nitrendipine (10 microM) or calciseptine (300 nM). In contrast, neither omega-agatoxin IVA (120 nM) nor omega-conotoxin GVIA (1 microM) affected this OA-induced increment significantly. We also evaluated the relationship between QC and extracellular [Ca2+] ([Ca2+]o) in BAPTA-AM-incubated MNT. Under conditions in which only P/Q-type VDCC were available to participate in neurotransmitter release, QC increased as [Ca2+]o was raised from 0.5 to 2 mM. However, when only L-type VDCC were available, QC increased when [Ca2+]o increased from 0.5 to 1 mM, but decreased significantly at 2 mM. The mean latency for P/Q-type VDCC-mediated EPP was 1.7-1.9 ms; for L-type VDCC-mediated EPP, 1.9-2.5 ms. The rise time of the L-type VDCC mediated EPP was significantly slower than that mediated by P/Q-type VDCC. Preincubation with H-7 (100 microM), a potent inhibitor of protein kinase C (PKC) and adenosine 3',5'cyclic monophosphate (cAMP)-dependent protein kinase (PKA), attenuated the OA-induced increment of both QC and MEPP frequency (50% and 70% decrement, respectively), suggesting the participation of at least these two protein kinases in the coupling of L-type VDCC. In summary, our results show coupling of L-type VDCC to neurotransmitter release when protein phosphatases are inhibited and intracellular [Ca2+] is buffered by the fast chelator BAPTA.
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PMID:Coupling of L-type calcium channels to neurotransmitter release at mouse motor nerve terminals. 1131 67