Diacylglycerol modulates action potential frequency in GH3 pituitary cells

correlative biochemical and electrophysiological studies

Charles M. Gammon, Gerry S. Oxford, Ann C. Allen, Ken D. McCarthy, Pierre Morell

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We have investigated the involvement of enhanced phosphoinositide metabolism in mediating TRH-induced alteration of electrophysiological events related to prolactin secretion by GH3 cells (a line of pituitary origin). Patch-clamp recording (in the current clamp, whole-cell configuration) showed that a few seconds after TRH application there was a brief period (about 30 s) of membrane hyperpolarization followed by several minutes of increased calcium-dependent action potential frequency. In parallel experiments cells were labeled for 24 h with either [3H]myo-inositol or [3H]arachidonate. Application of TRH resulted in rapid increases in levels of inositol phosphates and diacylglycerol. The time course of elevation of inositol 1,4,5-triphosphate (maximal by 5 s) is compatible with an initial burst of intracellular calcium mobilization associated with a transient phase of TRH-induced prolactin release. Application of TRH was also followed by a rapid but more sustained (several minutes) period of elevated diglyceride accumulation; a time course corresponding to a prolonged period of prolactin release which is dependent on the influx of external calcium. A causal relationship between diglyceride release and increased action potential frequency was demonstrated since local application (via a U-tube apparatus) of either 2 μM phorbol ester (phorbol 12,13-dibutyrate or phorbol 12-myristate 13-acetate) or 60 μM 1-oleoyl-2-acetyl-glycerol to patch-clamped cells could mimic this aspect of the TRH effect. In contrast, the inactive phorbol ester, 4α-phorbol, was unable to elicit this response. We suggest that the second (prolonged) phase of TRH-stimulated prolactin release involves phospholipase C-catalyzed formation of diglyceride with a resulting protein kinase C-mediated alteration of ion channel properties. These changes in channel properties lead to increased action potential frequency and a consequent influx of extracellular calcium.

Original languageEnglish (US)
Pages (from-to)217-224
Number of pages8
JournalBrain Research
Volume479
Issue number2
DOIs
StatePublished - Feb 13 1989
Externally publishedYes

Fingerprint

Diglycerides
Prolactin
Action Potentials
Calcium
Phorbol Esters
Phorbol 12,13-Dibutyrate
Inositol 1,4,5-Trisphosphate
Inositol Phosphates
Type C Phospholipases
Inositol
Phosphatidylinositols
Ion Channels
Protein Kinase C
Acetates
Cell Line
Membranes

Keywords

  • Action potential frequency
  • Diacylglycerol
  • GH cell
  • Inositol phosphate
  • Phorbol ester
  • Thyrotropin-releasing hormone

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Diacylglycerol modulates action potential frequency in GH3 pituitary cells : correlative biochemical and electrophysiological studies. / Gammon, Charles M.; Oxford, Gerry S.; Allen, Ann C.; McCarthy, Ken D.; Morell, Pierre.

In: Brain Research, Vol. 479, No. 2, 13.02.1989, p. 217-224.

Research output: Contribution to journalArticle

Gammon, Charles M. ; Oxford, Gerry S. ; Allen, Ann C. ; McCarthy, Ken D. ; Morell, Pierre. / Diacylglycerol modulates action potential frequency in GH3 pituitary cells : correlative biochemical and electrophysiological studies. In: Brain Research. 1989 ; Vol. 479, No. 2. pp. 217-224.
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