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Melanocortin receptors and δ‐opioid receptor mediate opposite signalling actions of POMC‐derived peptides in CATH.a cells
Author(s) -
René Frédérique,
Muller André,
Jover Emmanuel,
Kieffer Brigitte,
Koch Bernard,
Loeffler JeanPhilippe
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00199.x
Subject(s) - proopiomelanocortin , receptor , melanocortin , chemistry , medicine , second messenger system , endocrinology , biology , microbiology and biotechnology , biochemistry
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 (EC 50 : 4 × 10 –9 m ). 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 (EC 50 : 2.5 × 10 –8 m ), 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.