ArticleThe Journal of physiology2005
cAMP increases Ca2+-dependent exocytosis through both PKA and Epac2 in mouse melanotrophs from pituitary tissue slices.
Article in The Journal of physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 61 citations in OpenAlex.
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Epac2 Mediates cAMP-Dependent Potentiation of Neurotransmission in the Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Testing pancreatic islet function at the single cell level by calcium influx with associated marker expression.PloS one · 2015Article
- Structure-guided design of selective Epac1 and Epac2 agonists.PLoS biology · 2015Article
- Mechanisms of neuronal membrane sealing following mechanical trauma.Neuroscience bulletin · 2014Review
- cAMP-mediated stabilization of fusion pores in cultured rat pituitary lactotrophs.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Rab3a is critical for trapping alpha-MSH granules in the high Ca²⁺-affinity pool by preventing constitutive exocytosis.PloS one · 2013Article
- Glucose-stimulated calcium dynamics in islets of Langerhans in acute mouse pancreas tissue slices.PloS one · 2013Article
- Protein composition of immunoprecipitated synaptic ribbons.Journal of proteome research · 2012Article
- Pituitary growth hormone network responses are sexually dimorphic and regulated by gonadal steroids in adulthood.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Ion channels and signaling in the pituitary gland.Endocrine reviews · 2010Review
- A model for sealing plasmalemmal damage in neurons and other eukaryotic cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Epac activates the small G proteins Rap1 and Rab3A to achieve exocytosis.The Journal of biological chemistry · 2009Article
- EPAC proteins transduce diverse cellular actions of cAMP.British journal of pharmacology · 2009Review
- Application of an Epac activator enhances neurotransmitter release at excitatory central synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2008Article
- Molecular, pharmacological and functional properties of GABA(A) receptors in anterior pituitary cells.The Journal of physiology · 2008Article
- Epac and PKA: a tale of two intracellular cAMP receptors.Acta biochimica et biophysica Sinica · 2008Review
- Epac-selective cAMP analogs: new tools with which to evaluate the signal transduction properties of cAMP-regulated guanine nucleotide exchange factors.Cellular signalling · 2008Review
- Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Two cAMP-dependent pathways differentially regulate exocytosis of large dense-core and small vesicles in mouse beta-cells.The Journal of physiology · 2007Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclic AMP regulates Ca(2+)-dependent exocytosis through a classical protein kinase A (PKA)-dependent and an alternative cAMP-guanine nucleotide exchange factor (GEF)/Epac-dependent pathway in many secretory cells. Although increased cAMP is believed to double secretory output in isolated pituitary cells, the direct target(s) for cAMP action and a detailed and high-time resolved analysis of the effect of intracellular cAMP levels on the secretory activity in melanotrophs are still lacking. We investigated the effect of 200 microM cAMP on the kinetics of secretory vesicle depletion in mouse melanotrophs from fresh pituitary tissue slices. The whole-cell patch-clamp technique was used to depolarize melanotrophs and increase the cytosolic Ca(2+) concentration ([Ca(2+)](i)). Exogenous cAMP elicited an about twofold increase in cumulative membrane capacitance change and approximately 34% increase of high-voltage activated Ca(2+) channel amplitude. cAMP-dependent mechanisms did not affect [Ca(2+)](i), since the application of forskolin failed to change [Ca(2+)](i) in melanotrophs, a phenomenon readily observed in anterior lobe. Depolarization-induced secretion resulted in two distinct kinetic components: a linear and a threshold component, both stimulated by cAMP. The linear component (ATP-independent) probably represented the exocytosis of the release-ready vesicles, whereas the threshold component was assigned to the exocytosis of secretory vesicles that required ATP-dependent reaction(s) and > 800 nM [Ca(2+)](i). The linear component was modulated by 8-pCPT-2Me-cAMP (Epac agonist), while either H-89 (PKA inhibitor) or Rp-cAMPS (the competitive antagonist of cAMP binding to PKA) completely prevented the action of cAMP on the threshold component. In line with this, 6-Phe-cAMP, (PKA agonist), increased the threshold component. From our study, we suggest that the stimulation of cAMP production by application of oestrogen, as found in pregnant mice, increases the efficacy of the hormonal output through both PKA and cAMP-GEFII/Epac2-dependent mechanisms.
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