|Role of cAMP inhibition of p44/p42 mitogen-activated protein kinase in potentiation of protein secretion in rat lacrimal gland.|
|PMID: 17687004 Owner: NLM Status: MEDLINE|
|We previously found that addition of cAMP and a Ca(2+)/PKC-dependent agonist causes synergism or potentiation of protein secretion from rat lacrimal gland acini. In the present study we determined whether cAMP decreases p44/p42 mitogen-activated protein kinase (MAPK) activity in the lacrimal gland. Since we know that activation of MAPK attenuates protein secretion stimulated by Ca(2+)- and PKC-dependent agonists, we also determined whether this activation causes potentiation of secretion. Freshly prepared rat lacrimal gland acinar cells were incubated with dibutyryl cAMP (DBcAMP), carbachol (a cholinergic agonist), phenylephrine (an alpha(1)-adrenergic agonist), or epidermal growth factor (EGF). The latter three agonists are known to activate p44/p42 MAPK. p44/p42 MAPK activity and protein secretion were measured. As measured by Western blot analysis, DBcAMP inhibited both basal and agonist-stimulated p44/p42 MAPK activity. Cellular cAMP levels were increased by 1) using two different cell-permeant cAMP analogs, 2) activating adenylyl cyclase (L-858051), or 3) activation of G(s)-coupled receptors (VIP). The cell-permeant cAMP analogs, L-858051, and VIP inhibited basal p44/p42 MAPK activity by 50, 40, and 40%, respectively. DBcAMP and VIP inhibited carbachol- and EGF-stimulated MAPK activity. cAMP, but not VIP, inhibited phenylephrine-stimulated MAPK activity. Potentiation of secretion was detected when carbachol, phenylephrine, or EGF was simultaneously added with DBcAMP. We conclude that increasing cellular cAMP levels inhibits p44/p42 MAPK activity and that this could account for potentiation of secretion obtained when cAMP was elevated and Ca(2+) and PKC were increased by agonists.|
|Chika Funaki; Robin R Hodges; Darlene A Dartt|
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|Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural Date: 2007-08-08|
|Title: American journal of physiology. Cell physiology Volume: 293 ISSN: 0363-6143 ISO Abbreviation: Am. J. Physiol., Cell Physiol. Publication Date: 2007 Nov|
|Created Date: 2007-11-06 Completed Date: 2007-12-27 Revised Date: 2010-12-03|
Medline Journal Info:
|Nlm Unique ID: 100901225 Medline TA: Am J Physiol Cell Physiol Country: United States|
|Languages: eng Pagination: C1551-60 Citation Subset: IM|
|Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Adenylate Cyclase / metabolism
Adrenergic alpha-Agonists / pharmacology
Calcium / metabolism
Carbachol / pharmacology
Cholinergic Agonists / pharmacology
Cyclic AMP / metabolism*
Cyclic CMP / analogs & derivatives, metabolism
Dose-Response Relationship, Drug
Enzyme Activators / pharmacology
Epidermal Growth Factor / metabolism
Forskolin / analogs & derivatives, pharmacology
Lacrimal Apparatus / drug effects, enzymology, metabolism*
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors, metabolism*
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors, metabolism*
Peroxidases / secretion*
Phenylephrine / pharmacology
Phosphodiesterase Inhibitors / pharmacology
Phosphoric Diester Hydrolases / metabolism
Protein Kinase C / metabolism
Signal Transduction* / drug effects
Vasoactive Intestinal Peptide / metabolism
|EY06177/EY/NEI NIH HHS; R01 EY006177-26/EY/NEI NIH HHS|
|0/Adrenergic alpha-Agonists; 0/Cholinergic Agonists; 0/Enzyme Activators; 0/Phosphodiesterase Inhibitors; 110452-75-0/L 858051; 28822-58-4/1-Methyl-3-isobutylxanthine; 3616-08-8/Cyclic CMP; 37221-79-7/Vasoactive Intestinal Peptide; 51-83-2/Carbachol; 59-42-7/Phenylephrine; 60-92-4/Cyclic AMP; 62229-50-9/Epidermal Growth Factor; 64649-87-2/dibutyryl cyclic-3',5'-cytidine monophosphate; 66428-89-5/Forskolin; 7440-70-2/Calcium; EC 1.11.1.-/Peroxidases; EC 220.127.116.11/Protein Kinase C; EC 18.104.22.168/Mitogen-Activated Protein Kinase 1; EC 22.214.171.124/Mitogen-Activated Protein Kinase 3; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC 126.96.36.199/Adenylate Cyclase|
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