Document Detail


ZD7288 inhibits exocytosis in an HCN-independent manner and downstream of voltage-gated calcium influx in pituitary lactotrophs.
MedLine Citation:
PMID:  16780797     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pituitary lactotrophs fire action potentials spontaneously and the associated voltage-gated calcium influx is sufficient to maintain high prolactin release. Here we studied the role of hyperpolarization-activated cation channels in pacemaking activity, calcium signaling, and prolactin secretion in these cells. A slowly developing and hyperpolarization-activated inward current was identified but only in a fraction of lactotrophs. The current was blocked by ZD7288, a relatively specific blocker of these channels. However, the pacemaking activity increased in ZD7288-treated cells independently of the presence of this current. This in turn facilitated voltage-gated calcium influx and transiently stimulated prolactin secretion. Sustained ZD7288 application in concentrations that are commonly used to block the hyperpolarization-activated cation channels inhibited hormone release at elevated intracellular calcium concentrations. Agonist and Bay K 8644-stimulated prolactin release was also inhibited by ZD7288, indicating that this compound attenuates the exocytotic pathway downstream of calcium influx.
Authors:
Arturo E Gonzalez-Iglesias; Karla Kretschmannova; Melanija Tomic; Stanko S Stojilkovic
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2006-06-09
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  346     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-06-26     Completed Date:  2006-08-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  845-50     Citation Subset:  IM    
Affiliation:
Section on Cellular Signaling, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4510, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / metabolism*
Cations, Divalent / metabolism
Cells, Cultured
Cyclic Nucleotide-Gated Cation Channels
Electrophysiology
Exocytosis / drug effects*
Female
Ion Channels / metabolism*
Patch-Clamp Techniques
Pituitary Gland / cytology,  drug effects*,  metabolism*
Potassium Channels
Pyrimidines / pharmacology*
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Cations, Divalent; 0/Cyclic Nucleotide-Gated Cation Channels; 0/Ion Channels; 0/Potassium Channels; 0/Pyrimidines; 0/hyperpolarization-activated cation channel; 133059-99-1/ICI D2788; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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