Binding of CNP-22 and CNP-53 to cultured mouse astrocytes and effects on cyclic GMP.
We examined the binding characteristics of the two endogenous forms of C-type natriuretic peptide (CNP-22 and CNP-53) and their effects on cyclic GMP (cGMP) accumulation in primary cultures of mouse astrocytes. CNP-22 and CNP-53 competitively inhibited the specific binding of [125I][Tyr0]CNP, with an IC50 value of 32 and 37 pM, respectively. They also induced cGMP production in a dose-dependent and similar fashion, with an EC50 of 32 nM and maximal cGMP responses of 189.6 +/- 21.6 pmol/mg protein for CNP-22, and 170.3 +/- 18.7 pmol/mg protein for CNP-53, respectively. The effect of CNP-53 could not be explained by conversion to CNP-22, because HPLC analysis did not show significant proteolytic conversion by astrocytes during the incubation. Our results suggest that CNP-53 could, in concert with other natriuretic peptides, have a neuromodulatory function and thereby contribute to the central regulation of hemodynamic and fluid homeostasis.
Yeung
V T
VT
Department of Medicine, Chinese University of Hong Kong, Shatin.
Ho
S K
SK
Nicholls
M G
MG
Cockram
C S
CS
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006152:Cyclic GMP / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D020098:Natriuretic Peptide, C-Type; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology
D011506:Proteins; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP