Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To create precise neural circuits in the nervous system, neuritogenesis and synaptogenesis are the critical cellular processes during neuronal differentiation. We examined the cyclic AMP (cAMP)-responsible signaling pathways for regulating neuritogenesis and synaptogenesis in NG108-15 cells. A rise in intracellular cAMP concentration by a membrane-permeable cAMP analog, dibutyryl cAMP (DBcAMP), led to an increase in the number of neurites and varicosities. Inhibition of cAMP-dependent protein kinase (PKA) activity by a PKA inhibitor (H89) accelerated this neuritogenesis and neurite outgrowth rate. Treatment with H89, however, decreased the number of varicosities and the frequency of postsynaptic miniature current recorded in the cultured cells, resulting in suppression of synaptogenesis. Immunoblot analyses revealed that PKA activity mediates phosphorylation of a gene transcription factor, cAMP-response element binding protein (CREB). On the other hand, inhibition of a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway by a MAPK/ERK kinase (MEK) inhibitor (PD98059) suppressed both neuritogenesis and neurite outgrowth without CREB phosphorylation. These results suggest strongly that PKA simultaneously plays two different roles in neuronal differentiation: inhibition of neuritogenesis and stimulation of synaptogenesis, via CREB-mediated gene expression.
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PMID:Dual role of cyclic AMP-dependent protein kinase in neuritogenesis and synaptogenesis during neuronal differentiation. 1464 87

Endocannabinoids are well established as inhibitors of chemical synaptic transmission via presynaptic activation of the cannabinoid type 1 receptor (CB1R). Contrasting this notion, we show that dendritic release of endocannabinoids mediates potentiation of synaptic transmission at mixed (electrical and chemical) synaptic contacts on the goldfish Mauthner cell. Remarkably, the observed enhancement was not restricted to the glutamatergic component of the synaptic response but also included a parallel increase in electrical transmission. This effect involved the activation of CB1 receptors and was indirectly mediated via the release of dopamine from nearby varicosities, which in turn led to potentiation of the synaptic response via a cAMP-dependent protein kinase-mediated postsynaptic mechanism. Thus, endocannabinoid release can potentiate synaptic transmission, and its functional roles include the regulation of gap junction-mediated electrical synapses. Similar interactions between endocannabinoid and dopaminergic systems may be widespread and potentially relevant for the motor and rewarding effects of cannabis derivatives.
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PMID:Potentiation of electrical and chemical synaptic transmission mediated by endocannabinoids. 1809 17