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In vitro and in vivo characterization of bradykinin B2 receptors in the rabbit and the guinea pig.
Can J Physiol Pharmacol. 1996 Feb; 74(2):137-44.CJ

Abstract

A comparative study has been performed in isolated organs and in anesthetized animals, rabbits, and guinea pigs, to evaluated the myotropic responses (in the organs) and the blood pressure changes (in the animals) induced by bradykinin (BK) and related peptides. Antagonist affinities have also been estimated in vitro in terms of PA2 and in vivo in terms of ID50, to characterize the kinin B2 receptors in the two species. Differences have been found both in the order of potency of agonists and in the affinity of antagonists: in fact, in the rabbit, [Hyp3]BK > [Aib7]BK, is the opposite order of what is found in the guinea pig, namely, [Aib7]BK < [Hyp3]BK, both in vitro and in vivo. Results obtained with antagonists also show important differences between the two species, since DArg[Hyp3, DPhe7, Leu8]BK is more active in the rabbit than in the guinea pig, while WIN-64338 is fairly active in the guinea pig and almost inactive in the rabbit. HOE-140, the long-acting antagonist of the B2 receptor, shows similar affinities in vitro in the two species. In another series of experiments, peptide degradation by angiotensin converting enzyme (ACE) has been investigated to see whether the differences of potency observed between certain peptides interacting with the B2 receptor were due to metabolic degradation. When incubated in the presence of pure ACE from rabbit lung, BK,[Hyp3]BK, and des Arg9BK are readily degraded, while [Aib7]BK, HOE-140, and DArg[Hyp3, DPhe7, Leu8]BK are not. When applied intravenously (i.v.), to obtain degradation by the lung, and intraarterially (i.a.), to avoid such degradation, the effect of BK (i.v.) is markedly reduced (compared with the effect i.a.), while no difference is observed for [Aib7]BK. Thus, despite its resistance to degradation by ACE, [Aib7]BK shows very little activity in the rabbit, suggesting that the major cause in the variation of affinities observed between kinin analogs is related to their pharmacodynamic properties. Taken together, the results speak strongly in favor of the existence of B2 receptor subtypes in the peripheral circulation of the rabbit and the guinea pig. Results obtained in vivo, both in pharmacological and biochemical experiments, are in accord with the findings obtained in isolated organs and with purified ACE enzyme.

Authors+Show Affiliations

Department of Pharmacology, Medical School, Université de Sherbrooke, QC, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8723025

Citation

Gobeil, F, et al. "In Vitro and in Vivo Characterization of Bradykinin B2 Receptors in the Rabbit and the Guinea Pig." Canadian Journal of Physiology and Pharmacology, vol. 74, no. 2, 1996, pp. 137-44.
Gobeil F, Filteau C, Pheng LH, et al. In vitro and in vivo characterization of bradykinin B2 receptors in the rabbit and the guinea pig. Can J Physiol Pharmacol. 1996;74(2):137-44.
Gobeil, F., Filteau, C., Pheng, L. H., Jukic, D., Nguyen-Le, X. K., & Regoli, D. (1996). In vitro and in vivo characterization of bradykinin B2 receptors in the rabbit and the guinea pig. Canadian Journal of Physiology and Pharmacology, 74(2), 137-44.
Gobeil F, et al. In Vitro and in Vivo Characterization of Bradykinin B2 Receptors in the Rabbit and the Guinea Pig. Can J Physiol Pharmacol. 1996;74(2):137-44. PubMed PMID: 8723025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro and in vivo characterization of bradykinin B2 receptors in the rabbit and the guinea pig. AU - Gobeil,F, AU - Filteau,C, AU - Pheng,L H, AU - Jukic,D, AU - Nguyen-Le,X K, AU - Regoli,D, PY - 1996/2/1/pubmed PY - 1996/2/1/medline PY - 1996/2/1/entrez SP - 137 EP - 44 JF - Canadian journal of physiology and pharmacology JO - Can J Physiol Pharmacol VL - 74 IS - 2 N2 - A comparative study has been performed in isolated organs and in anesthetized animals, rabbits, and guinea pigs, to evaluated the myotropic responses (in the organs) and the blood pressure changes (in the animals) induced by bradykinin (BK) and related peptides. Antagonist affinities have also been estimated in vitro in terms of PA2 and in vivo in terms of ID50, to characterize the kinin B2 receptors in the two species. Differences have been found both in the order of potency of agonists and in the affinity of antagonists: in fact, in the rabbit, [Hyp3]BK > [Aib7]BK, is the opposite order of what is found in the guinea pig, namely, [Aib7]BK < [Hyp3]BK, both in vitro and in vivo. Results obtained with antagonists also show important differences between the two species, since DArg[Hyp3, DPhe7, Leu8]BK is more active in the rabbit than in the guinea pig, while WIN-64338 is fairly active in the guinea pig and almost inactive in the rabbit. HOE-140, the long-acting antagonist of the B2 receptor, shows similar affinities in vitro in the two species. In another series of experiments, peptide degradation by angiotensin converting enzyme (ACE) has been investigated to see whether the differences of potency observed between certain peptides interacting with the B2 receptor were due to metabolic degradation. When incubated in the presence of pure ACE from rabbit lung, BK,[Hyp3]BK, and des Arg9BK are readily degraded, while [Aib7]BK, HOE-140, and DArg[Hyp3, DPhe7, Leu8]BK are not. When applied intravenously (i.v.), to obtain degradation by the lung, and intraarterially (i.a.), to avoid such degradation, the effect of BK (i.v.) is markedly reduced (compared with the effect i.a.), while no difference is observed for [Aib7]BK. Thus, despite its resistance to degradation by ACE, [Aib7]BK shows very little activity in the rabbit, suggesting that the major cause in the variation of affinities observed between kinin analogs is related to their pharmacodynamic properties. Taken together, the results speak strongly in favor of the existence of B2 receptor subtypes in the peripheral circulation of the rabbit and the guinea pig. Results obtained in vivo, both in pharmacological and biochemical experiments, are in accord with the findings obtained in isolated organs and with purified ACE enzyme. SN - 0008-4212 UR - https://www.unboundmedicine.com/medline/citation/8723025/In_vitro_and_in_vivo_characterization_of_bradykinin_B2_receptors_in_the_rabbit_and_the_guinea_pig_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;PAGE=linkout&amp;SEARCH=8723025.ui DB - PRIME DP - Unbound Medicine ER -