Pituitary adenylate cyclase-activating polypeptide acts as a paracrine regulator of melatonin-responsive cells of the ovine pars tuberalis.
The pars tuberalis (PT) region of the anterior pituitary plays a physiological role in seasonal animals. The primary signal transduction mechanism of the melatonin receptor in this tissue is an inhibition of cAMP signaling. However, nothing is known about the endocrine signals that activate cAMP synthesis in the cells of the PT, as previous studies relied on the pharmacological tool, forskolin, to stimulate cAMP synthesis. Here we show that pituitary adenylate cyclase-activating polypeptide (PACAP) activates cAMP synthesis in the cells of the PT. The pharmacology of cAMP activation by PACAP peptides suggests that cAMP activation is mediated by the type I PACAP receptor. PACAP treatment of PT cells results in cellular responses that are consistent with cAMP activation in these cells, including activation of MAPK and elevation of melatonin receptor mt1 mRNA expression. These responses can be inhibited by melatonin, demonstrating that activation of cAMP occurs within the melatonin-responsive cells. However, although PACAP activates cAMP in the cells of the PT, the effect of PACAP may not be direct, as colocalization in situ hybridization studies demonstrates that the type I PACAP receptor and the melatonin mt1 receptor do not colocalize on the cells of the PT.
Barrett
Perry
P
Rowett Research Institute and Aberdeen Center for Energy Regulation and Obesity, Bucksburn, Aberdeen, United Kingdom AB21 9SB. pb@rri.sari.ac.uk
Messager
Sophie
S
Schuster
Carole
C
Moar
Kim M
KM
Mercer
Julian G
JG
Morgan
Peter J
PJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D002478:Cells, Cultured; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D017403:In Situ Hybridization; D008024:Ligands; D008550:Melatonin / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D019899:Paracrine Communication / Q000187:drug effects*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics; D044094:Receptors, Melatonin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep
D008024:Ligands; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases; D000262:Adenylyl Cyclases; D008550:Melatonin