W. Voelter et al., THE INTERACTION OF (1-4)-FRAGMENT OF THYMOSIN BETA-4 WITH CALMODULIN-SENSITIVE CAMP-PHOSPHODIESTERASE FROM HYPOTHALAMUS, Neurochemical research, 20(1), 1995, pp. 55-59
Evidence was accumulated indicating that cyclic nucleotides are involv
ed in regulation of growth, differentiation and function of lymphoid c
ells. It was previously shown that the N-fragment (1-4) of thymosin be
ta 4 (Ac-Ser-Asp-Lys-Pro-OH) inhibits in vivo the entry of cell popula
tions into S-phase. In the course of the study of the interrelationshi
p between the immune and neuroendocrine systems we have found that the
tetrapeptide caused incomplete competitive inhibition of hypothalamic
calmodulin (CaM)-dependent phosphodiesterase (PDE) stimulated by CaM.
In the presence of the peptide, the 20-fold increase of the constant
for PDE activation by CaM was accompanied by an insignificant rise in
the maximum rate of cAMP hydrolysis. The value of the inhibition const
ant (K-i) amounted to 600 nM. In the absence of CaM, the peptide at sa
turating concentrations reduced the basal activity of PDE nearly 2- to
3-fold. The effect of the peptide on PDE was noncompetitive with resp
ect to cAMP. The results support our suggestion that the tetrapeptide
realizes its effects in the immuno-neuroendocrine system by the mechan
ism of cyclic nucleotide metabolism.