Differential regulation of melatonin receptors in sheep, chicken and lizard brains by cholera and pertussis toxins and guanine nucleotides

Peter John Morgan, Lynda Williams, Perry Barrett, W Lawson, G Davidson, L Hannah, A MacLean

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

G-proteins define both the pharmacological characteristics and the signalling pathways of G-protein-coupled receptors. Melatonin receptors have been shown to belong to this class of receptors through their sensitivity to modulators of G-protein function. This study reveals that 2-I-125-iodomelatonin (I-125-MEL) binding to different target tissues is differentially affected by agents which disrupt the G-protein cycle. GTP gamma S, pertussis (PTX) and cholera (CTX) toxins each reduce I-125-MEL binding to ovine pars tuberalis (oPT) and lizard brain membranes, whereas chicken brain is affected only by GTP gamma S (guanosine 5'-O-(3-thiotriphosphate)) and CTX. In contrast, high affinity binding of I-125-MEL in the ovine hippocampus was not affected by any of these agents. This finding, together with the fact that neural binding sites of the sheep brain were found to have markedly lower molecular mass than those of the oPT on native gel electrophoresis (365 vs 525 kDa), suggests that the neural I-125-MEL binding sites in sheep may not be G-protein coupled. Pharmacologically, however, the binding sites in the hippocampus and oPT could not be distinguished using 11 analogues of melatonin. Therefore, these data support the notion not only of multiple forms of melatonin receptor/G-protein complex, but of high affinity binding sites for I-125-MEL which do not display sensitivity to guanine nucleotides.

Original languageEnglish
Pages (from-to)259-269
Number of pages11
JournalNeurochemistry International
Volume28
Issue number3
DOIs
Publication statusPublished - Mar 1996

Keywords

  • ovine pars tuberalis
  • adenylate-cyclase
  • binding-sites
  • signal transduction
  • ADP-ribosylation
  • G-protein
  • inhibition

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