Involvement of cAMP response element-binding protein activation in salivary secretion.
OBJECTIVE
Saliva secretion is mediated by cAMP and the calcium signaling pathway in salivary acinar cells. The PKA signaling pathway plays an important role in protein secretion through the activation of cAMP, in fluid secretion through the elevation of intracellular calcium and in the activation of cAMP response element-binding protein (CREB), which is involved in these signaling cascades. In this study, we investigated whether the activation of CREB plays a part in the salivary secretion in mice.


METHODS
We examined CREB activation by assessing phosphorylation at the serine-133 position using Western blotting.


RESULTS
Carbachol (a muscarinic acetylcholine agonist) and isoproterenol (a beta-adrenergic agonist) markedly activated CREB in parotid acinar cells. Carbachol and isoproterenol-induced CREB phosphorylation was blocked by atropine (a muscarinic acetylcholine antagonist) and propranolol (a beta-adrenergic antagonist), respectively. The PKA inhibitor H89 inhibited CREB activation, but the PLC inhibitor U73122 did not. Moreover, carbachol- and isoproterenol-stimulated amylase secretion from parotid acinar cells was inhibited by H89 and adenoviral dominant-negative CREB.


CONCLUSIONS
These results indicate that the muscarinic and beta-adrenergic activation of CREB was mediated through the PKA pathway and that CREB is involved in protein secretion from parotid acinar cells.
Yamada
Koichi
K
Department of Pathology, Tsurumi University School of Dental Medicine, Yokohama, Japan.
Inoue
Hiroko
H
Kida
Satoshi
S
Masushige
Shoichi
S
Nishiyama
Tatsuaki
T
Mishima
Kenji
K
Saito
Ichiro
I
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015153:Blotting, Western; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011433:Propranolol / Q000494:pharmacology; D012463:Saliva / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018679:Cholinergic Agonists; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D001285:Atropine; D002217:Carbachol; D011433:Propranolol; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol