Zd7288 Inhibits Exocytosis in an Hcn-independent Manner and Downstream of Voltage-gated Calcium Influx in Pituitary Lactotrophs.
From: 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.
Biochemical and biophysical research communications
- Publish Date: Aug 2006
- ISSN: 0006-291X
- Volume: 346
- Issue: 3
- Pages: 845-50
- Medium: Print
- Language: English
- Citation (JAMA): Gonzalez-Iglesias Arturo E, Kretschmannova Karla, Tomic Melanija, et al. Zd7288 Inhibits Exocytosis in an Hcn-independent Manner and Downstream of Voltage-gated Calcium Influx in Pituitary Lactotrophs.. Biochem. Biophys. Res. Commun. Aug 2006;346:845-50
Abstract
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.
Mesh Headings (Keywords): Animals, Calcium, Cations, Divalent, Cells, Cultured, Cyclic Nucleotide-Gated Cation Channels, Electrophysiology, Exocytosis, Female, Ion Channels, Patch-Clamp Techniques, Pituitary Gland, Potassium Channels, Pyrimidines, Rats, Rats, Sprague-Dawley
Check for Full Text / PubMed Unique Identifier (PMID): 16780797
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