Pharmacological profiles of the human and rabbit B1 receptors.

Gobeil, F; Neugebauer, W; Nguyen-Le, X K; Nea Allogho, S; Pheng, L H; Blouin, D; Whalley, E T; Regoli, D

Gobeil, F; Neugebauer, W; Nguyen-Le, X K; Nea Allogho, S; Pheng, L H; Blouin, D; Whalley, E T; Regoli, D.

Afiliación

Gobeil F; Department of Pharmacology, Medical School, Université de Sherbrooke, QC, Canada.

Can J Physiol Pharmacol ; 75(6): 591-5, 1997 Jun.

Article en En | MEDLINE | ID: mdl-9276134

RESUMEN

Twenty-two peptides related to kinins were used (i) to examine some chemical features required for the human and rabbit B1 receptor activation or blockade and (ii) to establish the existence of a correlation between the pharmacological spectrum of the B1 receptor obtained on the rabbit aorta (rbA) and the human umbilical vein (hUV). The apparent affinities of these peptides were measured in vitro using classical bioassays and are expressed in terms of pD2 (for agonists) or pA2 values (for antagonists). Selectivity for the B1 receptor was demonstrated by testing the peptides against the effect of bradykinin (BK) on the hUV and the rabbit jugular vein (rbJV), two preparations containing B2 receptor-mediating vasoconstriction. The results show that (i) lysyl-peptide agonists and antagonists demonstrate higher affinities than nonlysyl compounds on human and rabbit B1 receptors, (ii) peptides containing hydrophobic D-residues (e.g., Tic, beta Nal, Hyp(trans-propyl), Igl) in position 7 are suitable for B1 receptor antagonism, and (iii) the additive substitution of an Oic residue in position 8 leads to nonselective kinin receptor antagonists. Moreover, a high (r = 0.92) and positive (regression slope = 0.99 +/- 0.09) correlation between the affinities measured for the kinin analogues in two B1 receptor bioassay systems has been revealed. Based on the similarity of pharmacological profiles observed in the rabbit and human B1 receptors, we suggest that the B1 receptor domain in which peptide agonists and antagonists interact may be similar in these two species.

Asunto(s)

Antagonistas de los Receptores de Bradiquinina; Cininas/farmacología; Receptores de Bradiquinina/agonistas; Secuencia de Aminoácidos; Animales; Aorta/efectos de los fármacos; Aorta/ultraestructura; Humanos; Técnicas In Vitro; Cinética; Conejos; Receptor de Bradiquinina B1; Especificidad de la Especie; Relación Estructura-Actividad; Venas Umbilicales/efectos de los fármacos; Venas Umbilicales/ultraestructura

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Bradiquinina / Antagonistas de los Receptores de Bradiquinina / Cininas Límite: Animals / Humans Idioma: En Revista: Can J Physiol Pharmacol Año: 1997 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Canadá

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