Tonussi C R, Ferreira S H
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Eur J Pharmacol. 1997 May 12;326(1):61-5. doi: 10.1016/s0014-2999(97)00153-2.
The participation of B1 and B2 types of bradykinin receptors was studied in the rat knee-joint incapacitation test. Five intra-articular successive hourly administrations of bradykinin produced progressive incapacitation, thus indicating that bradykinin induced sensitization to its own nociceptive effect. Four co-injections of bradykinin with the bradykinin B1 receptor antagonist des-Arg9-[Leu8]bradykinin were without nociceptive effect. However, a 5th injection of bradykinin alone produced intense incapacitation. The bradykinin B2 receptor antagonist HOE-140 ([D-Arg)[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), or indomethacin, prevented the bradykinin-induced incapacitation. However, successive co-injections of bradykinin with prostaglandin E2, in contrast to bradykinin alone, did induce incapacitation in animals pretreated with indomethacin or HOE-140. The injection of the bradykinin B1 receptor agonist des-Arg9-bradykinin into prostaglandin E2-treated joints did induce incapacitation, although administration of the bradykinin B1 receptor agonist or prostaglandin E2 alone did not induce incapacitation. In conclusion, in ongoing articular inflammation, it is suggested that the bradykinin B1 receptor is particularly involved with nociceptor activation, while the bradykinin B2 receptor is related to nociceptor sensitization.
在大鼠膝关节失能试验中研究了B1和B2型缓激肽受体的参与情况。每小时关节内连续五次注射缓激肽会导致逐渐失能，从而表明缓激肽会诱导对其自身伤害性效应的敏化。四次将缓激肽与缓激肽B1受体拮抗剂去-Arg9-[Leu8]缓激肽共同注射没有伤害性效应。然而，单独第五次注射缓激肽会产生强烈失能。缓激肽B2受体拮抗剂HOE-140（[D-Arg][Hyp3,Thi5,D-Tic7,Oic8]缓激肽）或吲哚美辛可预防缓激肽诱导的失能。然而，与单独注射缓激肽相反，缓激肽与前列腺素E2连续共同注射确实会在预先用吲哚美辛或HOE-140处理的动物中诱导失能。将缓激肽B1受体激动剂去-Arg9-缓激肽注射到前列腺素E2处理的关节中确实会诱导失能，尽管单独给予缓激肽B1受体激动剂或前列腺素E2不会诱导失能。总之，在进行性关节炎症中，提示缓激肽B1受体特别参与伤害感受器的激活，而缓激肽B2受体与伤害感受器的敏化有关。
