Activation of guanylate cyclase by natriuretic peptides in mouse pituitary AtT20 cells is influenced by phosphorylation of ANP.
The discovery of free and membrane-bound ectokinases raises the question whether phosphorylation is another mechanism to modulate the action of distinct neuropeptides. Atrial-natriuretic-peptide (ANP) which is widespread found in the central nervous system (CNS) and involved in the modulation of stress reactions and emotional states like anxiety contains a recognition-motif for cAMP-dependent protein kinase A. We investigated the effect of phosphorylation of ANP and C-type natriuretic peptide (CNP), a related peptide without phosphorylation site, on their ability to activate their receptors in mouse pituitary AtT20 cells by measuring the formation of cyclic guanosinmonophosphate (cGMP). Phosphorylation with protein kinase A inactivated ANP. Coincubation experiments adding adenosintriphosphate (ATP), ATP-analogues or inhibitors of protein kinases to the medium pointed to the presence of an intrinsic protein kinase A like ectokinase-activity on AtT20 cells. The activity of CNP was unaffected in these experiments. Phosphorylation by ectokinases may be a physiological mechanism to regulate the biological activity of ANP in different tissues, such as pituitary and CNS.
Jahn
H
H
Clinic of Psychiatry and Psychotherapy, University of Hamburg, Germany. jahn@uke.uni-hamburg.de
Kiefer
F
F
Behl
C
C
Wiedemann
K
K
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D051379:Mice; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D010766:Phosphorylation; D010902:Pituitary Gland / Q000201:enzymology* / Q000473:pathology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D000255:Adenosine Triphosphate; D011494:Protein Kinases; C034454:ectoprotein kinase; D017868:Cyclic AMP-Dependent Protein Kinases; D006162:Guanylate Cyclase