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. 1987 Oct;92(2):333–340. doi: 10.1111/j.1476-5381.1987.tb11328.x

Effect of bradykinin antagonists on bradykinin-induced plasma extravasation, venoconstriction, prostaglandin E2 release, nociceptor stimulation and contraction of the iris sphincter muscle in the rabbit.

T Griesbacher 1, F Lembeck 1
PMCID: PMC1853661  PMID: 3479223

Abstract

1 The inhibition of the bradykinin-induced plasma extravasation by six bradykinin (Bk) antagonists was tested on rabbit skin. All of them showed inhibitory effects without an agonistic action in the does used. B4310 (Lys-Lys-3-Hyp-5,8-Thi-7-DPhe-Bk) was the most active antagonist and was therefore used in the subsequent experiments. 2 B4310 (5-500 nM) antagonized the bradykinin-induced reduction of the venous outflow from the rabbit isolated ear in dose-dependent manner without affecting the arterial vasoconstriction induced by angiotensin II. 3 The bradykinin-induced release of prostaglandin E2 (PGE2) from the perfused rabbit ear was reduced by 63% when B4310 (800 nM) was infused before, during and after the bradykinin injection. 4 Bradykinin was injected into the ear artery of anaesthetized rabbits and the reflex hypotensive response was used as indicator of the nociception. The response was antagonized by a local infusion of B4310 (50 and 500 nM). The antagonism was dose-dependent and reversible. The parallel shift of the dose-response curve to bradykinin suggests a competitive inhibition. However, B4310 did not antagonize acetylcholine-induced nociceptor stimulation. 5 B4310 inhibited bradykinin-induced stimulation of the trigeminal nerve which results in a substance P-mediated contraction of the iris sphincter muscle. A pA2 of 7.59 was calculated. B4310 did not inhibit capsaicin-induced contractions. 6 It is concluded that B4310 inhibits specifically five different actions of bradykinin which are related to its possible pathophysiological role.

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Selected References

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  1. Butler J. M., Hammond B. R. The effects of sensory denervation on the responses of the rabbit eye to prostaglandin E1, bradykinin and substance P. Br J Pharmacol. 1980 Jul;69(3):495–502. doi: 10.1111/j.1476-5381.1980.tb07040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chahl L. A. Interactions of bradykinin, prostaglandin E1, 5-hydroxytryptamine, histamine and adenosine-5'-triphosphate on the dry leakage response in rat skin. J Pharm Pharmacol. 1976 Oct;28(10):753–757. doi: 10.1111/j.2042-7158.1976.tb04041.x. [DOI] [PubMed] [Google Scholar]
  3. FOLKOW B., JOHANSSON B., MELLANDER S. The comparative effects of angiotensin and noradrenaline on consecutive vascular sections. Acta Physiol Scand. 1961 Oct;53:99–104. doi: 10.1111/j.1748-1716.1961.tb02267.x. [DOI] [PubMed] [Google Scholar]
  4. Gamse R., Holzer P., Lembeck F. Decrease of substance P in primary afferent neurones and impairment of neurogenic plasma extravasation by capsaicin. Br J Pharmacol. 1980 Feb;68(2):207–213. doi: 10.1111/j.1476-5381.1980.tb10409.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goldberg M. R., Chapnick B. M., Joiner P. D., Hyman A. L., Kadowitz P. J. Influence of inhibitors of prostaglandin synthesis on venoconstrictor responses to bradykinin. J Pharmacol Exp Ther. 1976 Aug;198(2):357–365. [PubMed] [Google Scholar]
  6. Juan H., Lembeck F. Action of peptides and other algesic agents on paravascular pain receptors of the isolated perfused rabbit ear. Naunyn Schmiedebergs Arch Pharmacol. 1974;283(2):151–164. doi: 10.1007/BF00501142. [DOI] [PubMed] [Google Scholar]
  7. Juan H. Mechanism of action of bradykinin-induced release of prostaglandin E. Naunyn Schmiedebergs Arch Pharmacol. 1977 Oct;300(1):77–85. doi: 10.1007/BF00505082. [DOI] [PubMed] [Google Scholar]
  8. Kern R. Die adrenergischen Receptoren der intraoculären Muskeln des Menschen. Eine in vitro-Studie. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1970;180(3):231–248. doi: 10.1007/BF00411532. [DOI] [PubMed] [Google Scholar]
  9. Lembeck F., Holzer P. Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn Schmiedebergs Arch Pharmacol. 1979 Dec;310(2):175–183. doi: 10.1007/BF00500282. [DOI] [PubMed] [Google Scholar]
  10. Lembeck F., Popper H., Juan H. Release of prostaglandins by bradykinin as an intrinsic mechanism of its algesic effect. Naunyn Schmiedebergs Arch Pharmacol. 1976 Jul;294(1):69–73. doi: 10.1007/BF00692786. [DOI] [PubMed] [Google Scholar]
  11. MILES A. A., MILES E. M. Vascular reactions to histamine, histamine-liberator and leukotaxine in the skin of guinea-pigs. J Physiol. 1952 Oct;118(2):228–257. doi: 10.1113/jphysiol.1952.sp004789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Marceau F., Knap M., Regoli D. Pharmacological characterization of the vascular permeability enhancing effects of kinins in the rabbit skin. Can J Physiol Pharmacol. 1981 Sep;59(9):921–926. doi: 10.1139/y81-142. [DOI] [PubMed] [Google Scholar]
  13. ROWLEY D. A. VENOUS CONSTRICTION AS THE CAUSE OF INCREASED VASCULAR PERMEABILITY PRODUCED BY 5-HYDROXYTRYPTAMINE, HISTAMINE, BRADYKININ AND 48/80 IN THE RAT. Br J Exp Pathol. 1964 Feb;45:56–67. [PMC free article] [PubMed] [Google Scholar]
  14. Regoli D., Barabé J. Pharmacology of bradykinin and related kinins. Pharmacol Rev. 1980 Mar;32(1):1–46. [PubMed] [Google Scholar]
  15. Regoli D., Drapeau G., Rovero P., Dion S., D'Orléans-Juste P., Barabé J. The actions of kinin antagonists on B1 and B2 receptor systems. Eur J Pharmacol. 1986 Apr 9;123(1):61–65. doi: 10.1016/0014-2999(86)90687-4. [DOI] [PubMed] [Google Scholar]
  16. SCHILD H. O. Drug antagonism and pAx. Pharmacol Rev. 1957 Jun;9(2):242–246. [PubMed] [Google Scholar]
  17. STERN P., NIKULIN A., FERLUGA J. The role of histamine and bradykinin in the inflammatory process. Arch Int Pharmacodyn Ther. 1962 Dec 1;140:528–538. [PubMed] [Google Scholar]
  18. Ueda N., Muramatsu I., Fujiwara M. Capsaicin and bradykinin-induced substance P-ergic responses in the iris sphincter muscle of the rabbit. J Pharmacol Exp Ther. 1984 Aug;230(2):469–473. [PubMed] [Google Scholar]
  19. Vavrek R. J., Stewart J. M. Competitive antagonists of bradykinin. Peptides. 1985 Mar-Apr;6(2):161–164. doi: 10.1016/0196-9781(85)90033-6. [DOI] [PubMed] [Google Scholar]

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