ABSTRACT
New analogues of atrial peptides of rat were synthesized by classical methods of peptide chemistry in solution. They contain a D-amino acid residue in the C-terminal part and a residue of mercaptopropionic acid in the N-terminal part of the molecule. Biological activity of the new analogues was studied.
Subject(s)
Atrial Natriuretic Factor/chemical synthesis , Amino Acid Sequence , Animals , Atrial Natriuretic Factor/metabolism , Atrial Natriuretic Factor/pharmacology , Diuresis/drug effects , Molecular Sequence Data , Potassium/urine , Rats , Sodium/urineABSTRACT
The effect of several synthetic FMRF-like peptides in hemodynamics and tonus of isolated rat vessels was studied. Peptide pGlu-Aps-Pro-Phe-Leu-Arg-Phe-NH2 and its C-terminal fragment Arg-Phe-NH2 induced i.v. short-term increase in arterial blood pressure and heart rate in narcotized rats. Benzpgexonium could reduce both effects of the drug. The peptide effect on blood pressure could be neutralized by prazosin; tachycardia could be prevented by propranolol. The studied peptide and its C-end tetra-, penta- and dipeptide produced relaxation of isolated rat aorta toned by prostaglandin F2 alpha. It is supposed that hypertensive effect of FMRF-like peptides is realized through central mechanisms.
Subject(s)
Blood Pressure/drug effects , Helix, Snails , Hypertension/etiology , Neuropeptides/adverse effects , Oligopeptides/adverse effects , Tissue Extracts/adverse effects , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiopathology , Culture Media , FMRFamide , In Vitro Techniques , Male , Neuropeptides/pharmacology , Oligopeptides/pharmacology , Rats , Rats, Inbred Strains , Tissue Extracts/pharmacologyABSTRACT
New FMRF-amide like peptide, pGlu-Asp-Pro-Phe-Leu-Arg-Phe-NH2, originally isolated from the ganglia of Helix aspersa, was synthetized. Intravenous injections of this peptide (40-300 micrograms/kg) produce rapid dose dependent increase in the blood pressure and heart rate of anaesthetised rats. Since alpha-adrenoreceptor blockade with prazosin eliminated pressor response, it is concluded that the increase in the arterial pressure is mediated by sympathetic activation.
Subject(s)
Blood Pressure/drug effects , Helix, Snails , Neuropeptides/pharmacology , Peptides/pharmacology , Animals , Dose-Response Relationship, Drug , Male , Neuropeptides/chemical synthesis , Peptides/chemical synthesis , Pyrrolidonecarboxylic Acid/analogs & derivatives , Rats , Rats, Inbred Strains , Stimulation, ChemicalABSTRACT
Pharmacokinetics of a new anti-ulcer drug, synthetic opioid hexapeptide dalargin (Tyr-D-Ala-Gly-Phe-Leu-Arg), which is an analogue of Leu-enkephalin, was studied in rats. Distribution and metabolism of 3H-Tyr-dalargin were examined after intravenous administration at a dose of 150 mg/kg. Main Tyr-containing metabolites of dalargin were detected and dynamics of their concentrations was evaluated in blood within 1 hr after administration. Kinetic curve of dalargin was described as three-exponential function.
Subject(s)
Anti-Ulcer Agents/pharmacokinetics , Enkephalin, Leucine-2-Alanine/analogs & derivatives , Enkephalin, Leucine/analogs & derivatives , Animals , Anti-Ulcer Agents/blood , Anti-Ulcer Agents/urine , Chromatography, High Pressure Liquid , Enkephalin, Leucine/blood , Enkephalin, Leucine/pharmacokinetics , Enkephalin, Leucine/urine , Male , Rats , Rats, Inbred Strains , Tissue DistributionABSTRACT
Comparative antihypertensive and natriuretic activities of atrial natriuretic factor (ANF) and its nearest shortened analogues--atriopeptines (AP) were studied in vivo on narcotized rats; and their peripheral vasodilating activities were studied in vitro on isolated rings of rat's thoracic aorta. The results obtained in vivo allow a following series of comparative antihypertensive and vasodilating activity: alpha rANF greater than APII greater than AP7-27. alpha rANF, APIII and APII did not differ significantly in vasodilating activity on isolated vessels; analogue 7-27 was less active. Thus further search of highly active shortened atriopeptin analogues is necessary for developing new drugs on their basis.
