Ca2+ signaling and exocytosis in pituitary corticotropes

Cell Calcium. 2012 Mar-Apr;51(3-4):253-9. doi: 10.1016/j.ceca.2011.12.007. Epub 2012 Jan 5.

Abstract

The secretion of adrenocorticotrophin (ACTH) from corticotropes is a key component in the endocrine response to stress. The resting potential of corticotropes is set by the basal activities of TWIK-related K(+) (TREK)-1 channel. Corticotrophin-releasing hormone (CRH), the major ACTH secretagogue, closes the background TREK-1 channels via the cAMP-dependent pathway, resulting in depolarization and a sustained rise in cytosolic [Ca(2+)] ([Ca(2+)](i)). By contrast, arginine vasopressin and norepinephrine evoke Ca(2+) release from the inositol trisphosphate (IP(3))-sensitive store, resulting in the activation of small conductance Ca(2+)-activated K(+) channels and hyperpolarization. Following [Ca(2+)](i) rise, cytosolic Ca(2+) is taken into the mitochondria via the uniporter. Mitochondrial inhibition slows the decay of the Ca(2+) signal and enhances the depolarization-triggered exocytotic response. Both voltage-gated Ca(2+) channel activation and intracellular Ca(2+) release generate spatial Ca(2+) gradients near the exocytic sites such that the local [Ca(2+)] is ~3-fold higher than the average [Ca(2+)](i). The stimulation of mitochondrial metabolism during the agonist-induced Ca(2+) signal and the robust endocytosis following stimulated exocytosis enable corticotropes to maintain sustained secretion during the diurnal ACTH surge. Arachidonic acid (AA) which is generated during CRH stimulation activates TREK-1 channels and causes hyperpolarization. Thus, corticotropes may regulate ACTH release via an autocrine feedback mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Arginine Vasopressin / metabolism
  • Calcium / metabolism*
  • Calcium Signaling*
  • Corticotrophs / physiology*
  • Corticotropin-Releasing Hormone / metabolism
  • Endocytosis
  • Excitation Contraction Coupling
  • Exocytosis
  • Feedback, Physiological
  • Humans
  • Ion Transport
  • Norepinephrine / metabolism

Substances

  • Arginine Vasopressin
  • Arachidonic Acid
  • Corticotropin-Releasing Hormone
  • Calcium
  • Norepinephrine