Intracellular signalling in the ovine pars tuberalis: an investigation using aluminium fluoride and melatonin

Peter John Morgan, M H HASTINGS, M THOMPSON, Perry Barrett, W LAWSON, G DAVIDSON

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Abstract

The effect of aluminium fluoride (AlF4-) has been studied on inositol phosphate accumulation, calcium mobilization, cyclic AMP production and [2-I-125]iodomelatonin binding in ovine pars tuberalis cells. These cells have high-affinity receptors for, and respond to, melatonin through inhibition of forskolin-stimulated adenylate cyclase. In the presence of 10 mM LiCl, AlF4- stimulated the net accumulation of inositol monophosphate and inositol bisphosphate. Consistent with these findings, AlF4- increased intracellular calcium; although this response was attenuated in calcium-depleted medium, indicating that the calcium response comprises both intracellular and extracellular components. Melatonin was ineffective on either basal or AlF4--stimulated turnover of inositol phosphates. In concordance with the inositol phosphate response, melatonin had no effect on either the AlF4--stimulated or the basal calcium levels. AlF4- blocked the increase in cyclic AMP stimulation by 1-mu-M forskolin, being as effective as melatonin, achieving approximately 90% inhibition. AlF4- also attenuated the binding of [2-I-125]iodomelatonin to ovine pars tuberalis membranes by 15%. At the concentration used, these results are consistent with the interpretation that AlF4- activates many G protein-mediated responses, and thus imply that the inhibitory pathway for cyclic AMP predominates over the stimulatory arm, whereas there can only be a stimulatory pathway linked to phosphoinositide metabolism in ovine pars tuberalis cells.

Original languageEnglish
Pages (from-to)137-144
Number of pages8
JournalJournal of Molecular Endocrinology
Volume7
Issue number2
DOIs
Publication statusPublished - Oct 1991

Keywords

  • guanine-nucleotides
  • G-proteins
  • receptors
  • inositol
  • brain
  • calcium
  • cyclase

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