THE INTERACTION OF (1-4)-FRAGMENT OF THYMOSIN BETA-4 WITH CALMODULIN-SENSITIVE CAMP-PHOSPHODIESTERASE FROM HYPOTHALAMUS

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.