Parathyroid hormone induces a calmodulin-dependent alteration in phosphodiesterase activity of rat kidney in vivo.
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.
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
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