Characterization of cAMP degradation by phosphodiesterases in the accessory olfactory system.
To characterize the potential role of cAMP in pheromone transduction, we have examined the occurrence of cyclic nucleotide phosphodiesterases (PDEs) in the mouse vomeronasal organ (VNO). We show that the cAMP-specific isoforms PDE4A and PDE4D are found preferentially in the apical and basal layers, respectively, of the VNO neuroepithelium and in the rostral (PDE4A) and caudal (PDE4D) portions of the accessory olfactory bulb glomerular layer. Assays for cAMP hydrolysis showed that PDE activity in VNO homogenates was about half that measured in the cerebral cortex and olfactory epithelium, and the proportion of total activity inhibited by rolipram, a PDE4-specific inhibitor, was approximately 40%. Activity in the VNO was enhanced 60% by Ca(2+) and calmodulin (CaM), implicating the presence of Ca(2+)/CaM-dependent PDE1. Zaprinast, which is known to inhibit PDE1C isoforms, completely suppressed Ca(2+)/CaM-stimulated activity and, together, zaprinast and rolipram inhibited cAMP hydrolysis by approximately 70%. Our results suggest that PDE1 and PDE4 isoforms are the primary source of cAMP degradation in the VNO.
Cherry
James A
JA
Department of Psychology, Boston University, 64 Cummington Street, Boston, MA 02215, USA. jcherry@bu.edu
Pho
Vanee
V
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006868:Hydrolysis; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D008297:Male; D051379:Mice; D009830:Olfactory Bulb / Q000166:cytology / Q000201:enzymology; D019147:Vomeronasal Organ / Q000166:cytology / Q000201:enzymology*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4