title: Parathyroid hormone induces a calmodulin-dependent alteration in phosphodiesterase activity of rat kidney in vivo.
abstract: In the basal state cyclic nucleotide phosphodiesterase in cytosol of rat kidney cortex is characterized by at least two kinetically distinct activities, with Michaelis-Menten constant (Km) for cAMP of 3.3 X 10(-6) and 3.7 X 10(-5) M. Eight minutes after in vivo injection of parathyroid extract, and persisting over 4 h, phosphodiesterase showed only one apparent activity, Km = approximately 1 X 10(-5) M. This change in kinetic profile was mimicked by the ip injection of 10 mg/kg (Bu)2-cAMP, and was reversed by incubation of cytosol with trifluoperazine or EGTA. Incubation of control cytosol with purified calmodulin duplicated the effect of hormone injection. Chromatography of control cytosol over diethylaminoethyl-cellulose resolved two activity peaks. Peak I, corresponding to the high Km activity of whole cytosol, was stimulated by calmodulin, representing a change in maximum velocity but not in substrate affinity. In addition, calmodulin stimulated the hydrolysis by Peak I of 3',5'-cyclic guanosine monophosphate. Peak II activity was not altered by calmodulin. These studies demonstrate that PTH promotes a rapid and sustained alteration in phosphodiesterase kinetics which is mediated by calcium and calmodulin, and which reflects the activation of the high Km component of the enzyme.
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D003600:Cytosol / Q000201:enzymology; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014020:Tissue Extracts / Q000494:pharmacology
chemical_list: D002135:Calcium-Binding Proteins; D002147:Calmodulin; D010281:Parathyroid Hormone; D014020:Tissue Extracts; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D015106:3',5'-Cyclic-GMP Phosphodiesterases