Melanocortin receptors and delta-opioid receptor mediate opposite signalling actions of POMC-derived peptides in CATH.a cells

Eur J Neurosci. 1998 May;10(5):1885-94. doi: 10.1046/j.1460-9568.1998.00199.x.


The locus coeruleus is innervated by proopiomelanocortin (POMC)-derived peptide immunoreactive fibres. The biological effects of ( melanocyte-stimulating hormone (aMSH) and [-endorphin on second messengers (cAMP, inositol phosphates) and gene transcription were studied in the locus cceruleus-derived cell line CATH.a. RT-PCR analysis revealed the presence of four MSH receptor subtypes (1, 3, 4 and 5). Activation of these receptors by diacetyl alphaMSH stimulated cAMP accumulation in a dose-dependent manner (EC50: 4 x 10(-9) M). Diacetyl alphaMSH stimulated transcription from reporter genes driven by the c-fos or tyrosine hydroxylase promoter. This effect was abolished when protein kinase A was inactivated with a dominant inhibitory mutant. RT-PCR analyses revealed the presence of delta-, but not mu-and kappa-opioid receptor. Pharmacological analysis showed that beta-endorphin (EC50: 2.5 x 10(-8)M), but not N-acetyl beta-endorphin, antagonized the biological effect of diacetyl alphaMSH on cAMP production and gene transcription. Since N-acetylation regulates the biological activity of alphaMSH and beta-endorphin in an opposite manner, we propose a model where the rate of secretion dictated by the bioelectric activity of the presynaptic neuron modulates POMC-derived peptide maturation and the resulting biological signal sensed by the postsynaptic plate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Cell Line
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Locus Coeruleus / cytology
  • Locus Coeruleus / physiology*
  • Logistic Models
  • Pro-Opiomelanocortin / physiology*
  • Proto-Oncogene Proteins c-fos / genetics
  • Receptors, Corticotropin / physiology*
  • Receptors, Melanocortin
  • Receptors, Opioid, delta / physiology*
  • Second Messenger Systems / physiology
  • Signal Transduction / physiology*
  • Transcription, Genetic
  • alpha-MSH / antagonists & inhibitors
  • alpha-MSH / pharmacology
  • beta-Endorphin / pharmacology


  • Proto-Oncogene Proteins c-fos
  • Receptors, Corticotropin
  • Receptors, Melanocortin
  • Receptors, Opioid, delta
  • alpha-MSH
  • beta-Endorphin
  • Pro-Opiomelanocortin
  • Cyclic AMP-Dependent Protein Kinases