HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Electrical properties of cultured human adrenocorticotropin-secreting adenoma cells: effects of high K+, corticotropin-releasing factor, and angiotensin II.

Abstract
ACTH-secreting pituitary adenoma cells were cultured from specimens obtained by transphenoidal hypophysectomy in five patients with Cushing's disease. The majority of adenoma cells (90%) stained specifically with antiserum against human ACTH. The electrophysiological properties and response to hormones of these cells were studied with intracellular recording techniques under current clamp and voltage clamp conditions. Most (80%) of the cells fired action potentials that were Ca2+-dependent inasmuch as they were blocked by Co2+ (5 mM) and by removal of Ca2+ from the medium, but were unaffected by tetrodotoxin (0.3 mM) and by Na+ removal. The cells responded to factors known to stimulate ACTH release, including high K+, CRF, and angiotensin II (AII). High K+ (50 mM) induced a membrane depolarization in association with an increase in conductance. CRF (100 nM) produced a depolarization, a decrease in conductance, an increase in spike firing, and an increase in spike duration. Although AII was inactive in ordinary recordings, in cells loaded with lithium (Li+) to promote the phospholipid-dependent second messenger system, the peptide produced an increase in spike firing and spike duration with no change in membrane potential. The combination of CRF and AII (CRF + AII; 100 nM each) in Li+-loaded cells caused a greater excitatory effect than either peptide alone. Under voltage clamp, the response either to CRF or to CRF + AII could be attributed, at least in part, to the inhibition of a slow, voltage-dependent K+ current that is persistently active at resting potential. These results indicate that modulation of action potential firing may be an early step in the regulation of ACTH release from pituitary cells by known secretagogues. Since action potentials in these cells are associated with Ca2+ entry, the resulting changes in intracellular Ca2+ levels could mediate the effects of the hormones on secretion.
AuthorsP Mollard, P Vacher, J Guerin, M A Rogawski, B Dufy
JournalEndocrinology (Endocrinology) Vol. 121 Issue 1 Pg. 395-405 (Jul 1987) ISSN: 0013-7227 [Print] United States
PMID3036472 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiotensin II
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Lithium
  • Potassium
  • Calcium
Topics
  • Action Potentials (drug effects)
  • Adenoma (physiopathology)
  • Adrenocorticotropic Hormone (metabolism)
  • Angiotensin II (pharmacology)
  • Calcium (pharmacology)
  • Corticotropin-Releasing Hormone (pharmacology)
  • Electric Conductivity
  • Electrophysiology
  • Humans
  • Lithium (pharmacology)
  • Membrane Potentials
  • Pituitary Neoplasms (physiopathology)
  • Potassium (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: