This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barrett, P. Articles by Morgan, P. J. Search for Related Content PubMed PubMed Citation Articles by Barrett, P. Articles by Morgan, P. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB 12-O-TETRADECANOYLPHORBOL-13-ACETATE

Mel 1a Melatonin Receptor Expression Is Regulated by Protein Kinase C and an Additional Pathway Addressed by the Protein Kinase C Inhibitor Ro 31–8220 in Ovine Pars Tuberalis Cells¹

Molecular Neuroendocrinology Group, Rowett Research Institute, Bucksburn, Aberdeen, Scotland AB21 9SB

Address all correspondence and requests for reprints to: Dr. Perry Barrett, Molecular Neuroendocrinology Group, Rowett Research Institute, Bucksburn, Aberdeen, Scotland AB21 9SB. E-mail: pb{at}rri.sari.ac.uk

The expression of the melatonin receptor is positively regulated by cAMP and negatively regulated by melatonin in the ovine pars tuberalis (PT). Furthermore, when PT cells are dispersed in primary culture, both messenger RNA (mRNA) and protein levels spontaneously increase through a process that can be blocked by melatonin, but does not involve cAMP. This suggests that other second messengers may be regulated by melatonin, which, in turn, regulates melatonin receptor mRNA and protein levels. In this study using ribonuclease protection assays, ligand binding, protein kinase C (PKC), and cAMP analysis, we demonstrate that the levels of Mel 1a mRNA and protein expression in ovine PT are reduced by phorbol 12-myristate 13-acetate in a cAMP-independent process. This is indicative of an inhibitory role for PKC in receptor regulation. Melatonin, however, does not act through PKC activation to reduce Mel 1a mRNA or protein levels. Basal PKC activity in PT cells can be inhibited by the PKC inhibitor Ro 31–8220, and this suggests that basal PKC activity may suppress Mel 1a receptor expression. Paradoxically, however, Ro 31–8220 also inhibits melatonin receptor mRNA and protein levels in PT cells by a cAMP-independent mechanism. This suggests that other undefined pathways must play an important role in the physiological self-regulation of Mel 1a receptor expression by melatonin.

This article has been cited by other articles:

				P. Barrett, S. Messager, C. Schuster, K. M. Moar, J. G. Mercer, and P. J. Morgan Pituitary Adenylate Cyclase-Activating Polypeptide Acts as a Paracrine Regulator of Melatonin-Responsive Cells of the Ovine Pars Tuberalis Endocrinology, June 1, 2002; 143(6): 2366 - 2375. [Abstract] [Full Text] [PDF]

				D. Roy and D. D. Belsham Melatonin Receptor Activation Regulates GnRH Gene Expression and Secretion in GT1-7 GnRH Neurons. SIGNAL TRANSDUCTION MECHANISMS J. Biol. Chem., January 4, 2002; 277(1): 251 - 258. [Abstract] [Full Text]

				P. BARRETT, W.-S. CHOI, M. MORRIS, and P. MORGAN A role for tyrosine phosphorylation in the regulation and sensitization of adenylate cyclase by melatonin FASEB J, August 1, 2000; 14(11): 1619 - 1628. [Abstract] [Full Text]

				L. Brydon, F. Roka, L. Petit, P. de Coppet, M. Tissot, P. Barrett, P. J. Morgan, C. Nanoff, A. D. Strosberg, and R. Jockers Dual Signaling of Human Mel1a Melatonin Receptors via Gi2, Gi3, and Gq/11 Proteins Mol. Endocrinol., December 1, 1999; 13(12): 2025 - 2038. [Abstract] [Full Text]