Melanocortin receptors and δ-opioid receptor mediate opposite signalling actions of POMC-derived peptides in CATH.a cells
Article first published online: 25 DEC 2001
European Journal of Neuroscience
Volume 10, Issue 5, pages 1885–1894, May 1998
How to Cite
René, F., Muller, A., Jover, E., Kieffer, B., Koch, B. and Loeffler, J.-P. (1998), Melanocortin receptors and δ-opioid receptor mediate opposite signalling actions of POMC-derived peptides in CATH.a cells. European Journal of Neuroscience, 10: 1885–1894. doi: 10.1046/j.1460-9568.1998.00199.x
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- Received 27 August 1997, revised 30 December 1997, accepted 19 January 1998
- second messengers;
The locus cœruleus is innervated by proopiomelanocortin (POMC)-derived peptide immunoreactive fibres. The biological effects of α melanocyte-stimulating hormone (αMSH) and β-endorphin on second messengers (cAMP, inositol phosphates) and gene transcription were studied in the locus cœruleus-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 αMSH stimulated cAMP accumulation in a dose-dependent manner (EC50: 4 × 10–9m). Diacetyl αMSH 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 δ-, but not μ-and κ-opioid receptor. Pharmacological analysis showed that β-endorphin (EC50: 2.5 × 10–8m), but not N-acetyl β-endorphin, antagonized the biological effect of diacetyl αMSH on cAMP production and gene transcription.
Since N-acetylation regulates the biological activity of αMSH and β-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.