RESUMO
Kinin-like properties of two new peptides NRP-11 and P7 which have structural similarity with neurotensin (NT) and kallidin (K) were investigated. It was found that, unlike NT and K, the new peptides possess reduced myotropic and hypotensive activity. On the other hand, similarly to NT and K, the new peptides exhibited a high histamine-releasing activity in rat peritoneal mast cells. Possible central effects are implied for peptide NRP-11 isolated from bovine brain and its fragment P7.
Assuntos
Calidina , Cininas , Neuropeptídeos , Neurotensina , Sequência de Aminoácidos , Animais , Bovinos , Cobaias , Liberação de Histamina , Calidina/farmacologia , Cininas/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Neuropeptídeos/farmacologia , Neurotensina/farmacologia , RatosRESUMO
Biological properties of a novel vasopressin analogue were investigated. It was found that this analogue has no vasopressor and oxytocic activities but it exhibits a selective antidiuretic effect which is weaker than that of adiuretin (DDAVP). Novel analogue inhibits vasopressor, oxytocic and antidiuretic effects caused by arginine--vasopressin. The usefulness of novel compound as a pharmacological tool--vasopressin antagonist is suggested.
Assuntos
Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/antagonistas & inibidores , Diuréticos/antagonistas & inibidores , Animais , Arginina Vasopressina/administração & dosagem , Arginina Vasopressina/farmacologia , Desamino Arginina Vasopressina/farmacologia , Feminino , Masculino , Ratos , Fatores de TempoRESUMO
Cyclic analogues of substance P of the formula cyclo-[Glu-Phe-Phe-Gly-Leu-Met-NH(CH2)nNH-], where n = 3-10, 12, and open-chain analogues (XVIIIa, b) H-Glu.(NHR)-Phe-Phe-Gly-Leu-Met-NHR, where R = -CH3, -CH2CH2CH3, were synthesized. By NMR spectroscopy it was found that cyclo-compounds with n = 3-8 have regularly arranged structures, stabilized by intramolecular hydrogen bonds. Substances of this type showed less than or equal to 0.1% of the substance P activity on the guinea pig ileum, but some of them antagonize the natural peptide (for compound with n = 5 IC50 = 3.2.10(-6) M). The open-chain compounds proved to have rather high myotropic activity, viz., 22% (R = -CH3) and 8% (R = -CH2CH2CH3) of the substance P activity.
Assuntos
Substância P/análogos & derivados , Animais , Cobaias , Íleo/efeitos dos fármacos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Conformação Proteica , Substância P/antagonistas & inibidoresRESUMO
1 alpha-beta-carboxypropionyl-cyclo(9----1 epsilon)-[Lys1, Gly6]bradykinin (Suc-c[Lys1, Gly6]B), 1 alpha-beta-carboxypropionyl-cyclo(10----1 epsilon)kallidin (Suc-cK), cyclo(10 gamma----1 epsilon)-[Glu10]kallidin (c[Glu10]K) and cyclo(11 gamma----1 epsilon)kallidylglutamic acid (cKG) were synthesized. Suc-c[Lys1, Gly6]B and Suc-cK were prepared by acylating the appropriate cyclopeptides with succinic anhydride. c[Glu10]K and cKG were obtained by the classic peptide synthesis, the cyclization being carried out with 61 and 42% yields, respectively. The protecting groups were then eliminated by catalytic hydrogenation. c[Glu10]K and cKG exerted myotropic action on isolated rat uterus (alpha 0.73 and 0.89, pD2 6.61 and 8.61, respectively). cKG displayed direct myotropic activity with respect to electrically stimulated rat vas deferens and guinea-pig ileum, potentiating the contractions (by 100%) in response to electric stimuli. c[Glu10]K and cKG elicit histamine release in isolated rat mast cells (EC30 4.91.10(-5) and 1.47.10(-6) M, respectively). Both cyclopeptides alter arterial pressure following intravenous administration to anaesthetized rats, cats and dogs and affect heart rate. In all assays cKG is more active than c[Glu10]K. Suc-c[Lys1, Gly6]B and Suc-cK do not possess myotropic, histamine-releasing or hypotensive activity, though they were found to elicit a transient increase of bloodflow in cats and dogs.