Gene/Protein
Disease
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Drug
Enzyme
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Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:4.6.1.1 (
adenylate cyclase
)
19,190
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Intestinal mucosal as well as extramucosal antibody responses were studied in mice after peroral immunizations with cholera toxin or cholera B subunit. The immunizations with cholera toxin gave rise to a marked response with antitoxin-secreting cells (
PFC
) in Peyer's patches (PP), mesenteric lymph nodes (MLN) and spleen showing isotype distribution of IgG greater than IgA greater than IgM and with
PFC
kinetics in MLN and spleen that suggested migration of cells from PP after peroral administration rather than cells stimulated in situ by adsorbed antigen. Highest numbers of
PFC
were obtained after 2 immunizations, and further administrations resulted in a decrease in the
PFC
response in MLN and spleen, while the PP responsiveness was relatively unchanged, and interestingly, protective immunity and IgA-dominated antitoxin titers in intestinal washings increased markedly by the additional boosters. Animals immunized with cholera B subunit, which lacks the
adenylate cyclase
-stimulating capacity of cholera toxin, showed similar
PFC
responses in extramucosal organs as those receiving cholera toxin but were poorly protected and had correspondingly lower IgA antitoxin titers in intestinal washings. These results suggest that the mucosal IgA antitoxin predominance is mainly due to regulatory mechanisms operating on the end-stage differentiation of the committed B cells in lamina propria and that this differentiation, as judged from the different results with cholera toxin and its B subunit, might be influenced by cyclic AMP.
...
PMID:IgA isotype restriction in the mucosal but not in the extramucosal immune response after oral immunizations with cholera toxin or cholera B subunit. 687 6
Stimulation of alpha(2)-noradrenergic (NA) receptors within the
PFC
improves working memory performance. This improvement is accompanied by a selective increase in the activity of
PFC
neurons during delay periods, although the cellular mechanisms responsible for this enhanced response are largely unknown. Here we used current and voltage clamp recordings to characterize the response of layer V-VI
PFC
pyramidal neurons to alpha(2)-NA receptor stimulation. alpha(2)-NA receptor activation produced a small hyperpolarization of the resting membrane potential, which was accompanied by an increase in input resistance and evoked firing. Voltage clamp analysis demonstrated that alpha(2)-NA receptor stimulation inhibited a caesium and ZD7288-sensitive hyperpolarization-activated (HCN) inward current. Suppression of HCN current by alpha(2)-NA stimulation was not dependent on
adenylate cyclase
but instead required activation of a PLC-PKC linked signalling pathway. Similar to direct blockade of HCN channels, alpha(2)-NA receptor stimulation produced a significant enhancement in temporal summation during trains of distally evoked EPSPs. These dual effects of alpha(2)-NA receptor stimulation - membrane hyperpolarization and enhanced temporal integration - together produce an increase in the overall gain of the response of
PFC
pyramidal neurons to excitatory synaptic input. The net effect is the suppression of isolated excitatory inputs while enhancing the response to a coherent burst of synaptic activity.
...
PMID:alpha2-Noradrenergic receptors activation enhances excitability and synaptic integration in rat prefrontal cortex pyramidal neurons via inhibition of HCN currents. 1770 9
The aim of this perforated-patch study was to test the effect of isoproterenol on the membrane potential in mPFC (medial prefrontal cortex) pyramidal neurons. Isoproterenol depolarized the membrane potential recorded from the soma. This effect was absent in the presence of metoprolol, suggesting the involvement of beta1-adrenergic receptors. The
adenylate cyclase
activator forskolin also depolarized the membrane potential. Moreover, the effect of isoproterenol was abolished by the
adenylate cyclase
inhibitor SQ 22536. This suggested that
adenylate cyclase
was involved in mediating the effect of the beta-adrenergic receptor agonist. The isoproterenol-induced depolarization persisted after inhibition of protein kinase A with H-89. The effect of beta-adrenergic receptor activation on the membrane potential was dependent on Ih channels because it was abolished in the presence of the Ih channel inhibitor ZD 7288. Dendritic recordings were also performed. In the dendritic segments between 100 microm and 150 microm from the soma and between 200 microm and 250 microm from the soma, isoproterenol also depolarized the membrane potential. The magnitude of the beta-adrenergic receptor-stimulated depolarization was the same in the soma and in both dendritic localizations. The depolarization exerted by isoproterenol may influence
PFC
cognitive functions.
...
PMID:Somatic and dendritic perforated-patch recordings reveal b-adrenergic receptor-induced depolarization in medial prefrontal cortex pyramidal neurons. 2737 53
Using a genetic mouse model that faithfully recapitulates a
DISC1
genetic alteration strongly associated with schizophrenia and other psychiatric disorders, we examined the impact of this mutation within the prefrontal cortex. Although cortical layering, cytoarchitecture, and proteome were found to be largely unaffected, electrophysiological examination of the mPFC revealed both neuronal hyperexcitability and alterations in short-term synaptic plasticity consistent with enhanced neurotransmitter release. Increased excitability of layer II/III pyramidal neurons was accompanied by consistent reductions in voltage-activated potassium currents near the action potential threshold as well as by enhanced recruitment of inputs arising from superficial layers to layer V. We further observed reductions in both the paired-pulse ratios and the enhanced short-term depression of layer V synapses arising from superficial layers consistent with enhanced neurotransmitter release at these synapses. Recordings from layer II/III pyramidal neurons revealed action potential widening that could account for enhanced neurotransmitter release. Significantly, we found that reduced functional expression of the voltage-dependent potassium channel subunit K
v
1.1 substantially contributes to both the excitability and short-term plasticity alterations that we observed. The underlying dysregulation of K
v
1.1 expression was attributable to cAMP elevations in the
PFC
secondary to reduced phosphodiesterase 4 activity present in Disc1 deficiency and was rescued by pharmacological blockade of
adenylate cyclase
. Our results demonstrate a potentially devastating impact of Disc1 deficiency on neural circuit function, partly due to K
v
1.1 dysregulation that leads to a dual dysfunction consisting of enhanced neuronal excitability and altered short-term synaptic plasticity.
SIGNIFICANCE STATEMENT
Schizophrenia is a profoundly disabling psychiatric illness with a devastating impact not only upon the afflicted but also upon their families and the broader society. Although the underlying causes of schizophrenia remain poorly understood, a growing body of studies has identified and strongly implicated various specific risk genes in schizophrenia pathogenesis. Here, using a genetic mouse model, we explored the impact of one of the most highly penetrant schizophrenia risk genes,
DISC1
, upon the medial prefrontal cortex, the region believed to be most prominently dysfunctional in schizophrenia. We found substantial derangements in both neuronal excitability and short-term synaptic plasticity-parameters that critically govern neural circuit information processing-suggesting that similar changes may critically, and more broadly, underlie the neural computational dysfunction prototypical of schizophrenia.
...
PMID:Alteration of Neuronal Excitability and Short-Term Synaptic Plasticity in the Prefrontal Cortex of a Mouse Model of Mental Illness. 2828 61
