ABSTRACT
We investigated the influence of tuftsin partial sequences (Thr-Lys, Lys-Pro, Lys-Pro-Arg and Pro-Arg) on histamine concentration in selected tissues (lungs, kidneys, liver, duodenal wall and arterial blood) of guinea-pigs and rats. The peptides were administered in 1 mg/kg dose intravenously (single dose) or intraperitoneally (single dose or three doses at one-hour intervals). Histamine concentration was determined spectrofluorimetrically. Tissues used in the determination were taken 1 hour after the last injection. It was found that Pro-Arg and Lys-Pro-Arg (similarly to tuftsin), lower histamine concentration in lungs, and elevate it in kidneys.
Subject(s)
Histamine/metabolism , Peptide Fragments/pharmacology , Tuftsin/pharmacology , Amino Acid Sequence , Animals , Guinea Pigs , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Lung/drug effects , Lung/metabolism , Molecular Sequence Data , Peptide Fragments/administration & dosage , Peptide Fragments/chemistry , Rats , Rats, Wistar , Structure-Activity Relationship , Tissue Distribution , Tuftsin/administration & dosage , Tuftsin/chemistryABSTRACT
C-Terminal dipeptide fragment of tuftsin, Pro-Arg, substituted by D-amino acids, and tuftsin analogs with n-hexyl- and n-heptylamine coupled to their C-termini were synthesized by a classical method in solution and their antinociceptive activity was measured by tail flick immersion test (0.4 microM/icv). D-Pro-D-Arg and D-Pro-L-Arg showed an analgesic activity, with the duration of 60 and 40 min, respectively. The strong behavioral effects observed after injection of D-Pro-D-Arg were decreased by naloxone. L-Pro-D-Arg and Thr-Lys-Pro-Arg-HxA display no antinociceptive effect; the tetrapeptide amide showed some toxicity effects. Thr-Lys-Pro-Arg-HpA was very toxic and caused death of all experimental animals. This effect was not influenced by previous injection of naloxone.
Subject(s)
Analgesics/pharmacology , Dipeptides/pharmacology , Peptide Fragments/pharmacology , Tuftsin/analogs & derivatives , Amino Acid Sequence , Animals , Behavior, Animal/drug effects , Male , Molecular Sequence Data , Motor Activity/drug effects , Naloxone/pharmacology , Rats , Rats, Inbred Strains , Tuftsin/chemistry , Tuftsin/pharmacology , Tuftsin/toxicityABSTRACT
The immunomodulatory potency of a series of proline-containing thymopentin (TP-5) analogues was investigated by PFC (in vitro and in vivo) test and by GvH reaction. It was found that the substitution of Asp in position 3 of TP-5 by D-Pro yields a distinctly more active compound than that obtained by substitution of Asp3 by L-Pro. Pro5-TP-5 showed very strongly enhanced activity as compared with TP-5; the effect is especially well obvious in PFC in vitro (15-fold enhancement of activity).
