A novel interaction between inhibitory melatonin receptors and protein kinase C-dependent signal transduction in ovine pars tuberalis cells

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

This study revealed an important and unexpected finding: namely, that inhibitory melatonin receptors can inhibit a phorbol 12,13 myristate acetate (PMA)-induced, protein kinase C (PKC)-dependent increase in c-fos messenger RNA expression in ovine pars tuberalis (PT) cells. PMA induces dose-dependent stimulation of c-fos expression that is attenuated by melatonin in a dose-dependent and pertussis toxin-sensitive manner. The effect of 100 nar PMA is blocked by Ro31-8220 (1 mu M), yet is not mimicked by 4 alpha-PMA (100 nM). PMA (100 nM) induces PKC activity in PT cells (P < 0.05) within 5 min, but melatonin has no effect on this response. PMA (100 nM) stimulates both phospholipase D and mitogen-activated protein kinase (MAPK) (p42/44) activities in PT cells, but melatonin has no effect on these responees. The results indicate that neither of these second-messenger activities contribute to the melatonin-sensitive pathway of c-fos activation. The MEK (MAPK kinase) inhibitor, PD98059 (50 mu M), does not block the induction of c-ibs by PMA, although at the same dose it inhibits PMA-mediated activation of p42/44 MAPK by 50-70%, and activation by forskolin or insulin-like growth factor-I by 100%. These data suggest that p42/44 MAPK may not be the primary mediator of PKC-dependent c-fos induction. In contrast to the effect of melatonin on PMA-mediated c-fos induction in PT cells, in L cells stably transfected with the sheep Mel1a beta receptor, melatonin potentiates the c-fos response in a pertussis toxin-sensitive manner. These data indicate the tissue-specific nature of melatonin receptor signaling, and reveal that a pertussis toxin-sensitive pathway can block PKC-mediated c-fos induction in PT cells.

Original languageEnglish
Pages (from-to)1723-1730
Number of pages8
JournalEndocrinology
Volume139
Issue number4
DOIs
Publication statusPublished - Apr 1998

Keywords

  • pituitary-cells
  • expression
  • rams
  • activation
  • secretion
  • prolactin
  • forskolin
  • mechanism
  • cloning
  • nucleus

Cite this

@article{6e5e8d52214949468904698f87161fd3,
title = "A novel interaction between inhibitory melatonin receptors and protein kinase C-dependent signal transduction in ovine pars tuberalis cells",
abstract = "This study revealed an important and unexpected finding: namely, that inhibitory melatonin receptors can inhibit a phorbol 12,13 myristate acetate (PMA)-induced, protein kinase C (PKC)-dependent increase in c-fos messenger RNA expression in ovine pars tuberalis (PT) cells. PMA induces dose-dependent stimulation of c-fos expression that is attenuated by melatonin in a dose-dependent and pertussis toxin-sensitive manner. The effect of 100 nar PMA is blocked by Ro31-8220 (1 mu M), yet is not mimicked by 4 alpha-PMA (100 nM). PMA (100 nM) induces PKC activity in PT cells (P < 0.05) within 5 min, but melatonin has no effect on this response. PMA (100 nM) stimulates both phospholipase D and mitogen-activated protein kinase (MAPK) (p42/44) activities in PT cells, but melatonin has no effect on these responees. The results indicate that neither of these second-messenger activities contribute to the melatonin-sensitive pathway of c-fos activation. The MEK (MAPK kinase) inhibitor, PD98059 (50 mu M), does not block the induction of c-ibs by PMA, although at the same dose it inhibits PMA-mediated activation of p42/44 MAPK by 50-70{\%}, and activation by forskolin or insulin-like growth factor-I by 100{\%}. These data suggest that p42/44 MAPK may not be the primary mediator of PKC-dependent c-fos induction. In contrast to the effect of melatonin on PMA-mediated c-fos induction in PT cells, in L cells stably transfected with the sheep Mel1a beta receptor, melatonin potentiates the c-fos response in a pertussis toxin-sensitive manner. These data indicate the tissue-specific nature of melatonin receptor signaling, and reveal that a pertussis toxin-sensitive pathway can block PKC-mediated c-fos induction in PT cells.",
keywords = "pituitary-cells, expression, rams, activation, secretion, prolactin, forskolin, mechanism, cloning, nucleus",
author = "Alexander Ross and Webster, {C A} and M Thompson and Perry Barrett and Morgan, {Peter John}",
year = "1998",
month = "4",
doi = "10.1210/en.139.4.1723",
language = "English",
volume = "139",
pages = "1723--1730",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - A novel interaction between inhibitory melatonin receptors and protein kinase C-dependent signal transduction in ovine pars tuberalis cells

AU - Ross, Alexander

AU - Webster, C A

AU - Thompson, M

AU - Barrett, Perry

AU - Morgan, Peter John

PY - 1998/4

Y1 - 1998/4

N2 - This study revealed an important and unexpected finding: namely, that inhibitory melatonin receptors can inhibit a phorbol 12,13 myristate acetate (PMA)-induced, protein kinase C (PKC)-dependent increase in c-fos messenger RNA expression in ovine pars tuberalis (PT) cells. PMA induces dose-dependent stimulation of c-fos expression that is attenuated by melatonin in a dose-dependent and pertussis toxin-sensitive manner. The effect of 100 nar PMA is blocked by Ro31-8220 (1 mu M), yet is not mimicked by 4 alpha-PMA (100 nM). PMA (100 nM) induces PKC activity in PT cells (P < 0.05) within 5 min, but melatonin has no effect on this response. PMA (100 nM) stimulates both phospholipase D and mitogen-activated protein kinase (MAPK) (p42/44) activities in PT cells, but melatonin has no effect on these responees. The results indicate that neither of these second-messenger activities contribute to the melatonin-sensitive pathway of c-fos activation. The MEK (MAPK kinase) inhibitor, PD98059 (50 mu M), does not block the induction of c-ibs by PMA, although at the same dose it inhibits PMA-mediated activation of p42/44 MAPK by 50-70%, and activation by forskolin or insulin-like growth factor-I by 100%. These data suggest that p42/44 MAPK may not be the primary mediator of PKC-dependent c-fos induction. In contrast to the effect of melatonin on PMA-mediated c-fos induction in PT cells, in L cells stably transfected with the sheep Mel1a beta receptor, melatonin potentiates the c-fos response in a pertussis toxin-sensitive manner. These data indicate the tissue-specific nature of melatonin receptor signaling, and reveal that a pertussis toxin-sensitive pathway can block PKC-mediated c-fos induction in PT cells.

AB - This study revealed an important and unexpected finding: namely, that inhibitory melatonin receptors can inhibit a phorbol 12,13 myristate acetate (PMA)-induced, protein kinase C (PKC)-dependent increase in c-fos messenger RNA expression in ovine pars tuberalis (PT) cells. PMA induces dose-dependent stimulation of c-fos expression that is attenuated by melatonin in a dose-dependent and pertussis toxin-sensitive manner. The effect of 100 nar PMA is blocked by Ro31-8220 (1 mu M), yet is not mimicked by 4 alpha-PMA (100 nM). PMA (100 nM) induces PKC activity in PT cells (P < 0.05) within 5 min, but melatonin has no effect on this response. PMA (100 nM) stimulates both phospholipase D and mitogen-activated protein kinase (MAPK) (p42/44) activities in PT cells, but melatonin has no effect on these responees. The results indicate that neither of these second-messenger activities contribute to the melatonin-sensitive pathway of c-fos activation. The MEK (MAPK kinase) inhibitor, PD98059 (50 mu M), does not block the induction of c-ibs by PMA, although at the same dose it inhibits PMA-mediated activation of p42/44 MAPK by 50-70%, and activation by forskolin or insulin-like growth factor-I by 100%. These data suggest that p42/44 MAPK may not be the primary mediator of PKC-dependent c-fos induction. In contrast to the effect of melatonin on PMA-mediated c-fos induction in PT cells, in L cells stably transfected with the sheep Mel1a beta receptor, melatonin potentiates the c-fos response in a pertussis toxin-sensitive manner. These data indicate the tissue-specific nature of melatonin receptor signaling, and reveal that a pertussis toxin-sensitive pathway can block PKC-mediated c-fos induction in PT cells.

KW - pituitary-cells

KW - expression

KW - rams

KW - activation

KW - secretion

KW - prolactin

KW - forskolin

KW - mechanism

KW - cloning

KW - nucleus

U2 - 10.1210/en.139.4.1723

DO - 10.1210/en.139.4.1723

M3 - Article

VL - 139

SP - 1723

EP - 1730

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 4

ER -