ZD7288 inhibits exocytosis in an HCN-independent manner and downstream of voltage-gated calcium influx in pituitary lactotrophs.

Biochem Biophys Res Commun

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.

Published: August 2006

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.

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http://dx.doi.org/10.1016/j.bbrc.2006.05.194DOI Listing

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