ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1460-9568.1998.00199.x
