Reduction of sodium deoxycholic acid-induced scratching behaviour by bradykinin B2 receptor antagonists

Authors


Department of Pharmacology, Kitasato University School of Medicine, 1–15-1 Kitasato, Sagami-hara-shi, Kanagawa 228–8555, Japan. E-mail: hayashii@med.kitasato-u.ac.jp.

Abstract

  • Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws.

  • Up to 100 μg of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method.

  • Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid.

  • Treatment with aprotinin to inhibit tissue kallikrein reduced the scratching behaviour induced by sodium deoxycholic acid, whereas treatment with soybean trypsin inhibitor to inhibit plasma kallikrein did not.

  • Although injection of kininase II inhibitor, lisinopril together with sodium deoxycholic acid did not alter the scratching behaviour, phosphoramidon, a neutral endopeptidase inhibitor, significantly increased the frequency of scratching.

  • Homogenates of the skin excised from the backs of mice were subjected to gel-filtration column chromatography followed by an assay of kinin release by trypsin from each fraction separated. Less kinin release from the fractions containing kininogen of low molecular weight was observed in the skin injected with sodium deoxycholic acid than in normal skin.

  • The frequency of scratching after the injection of sodium deoxycholic acid in plasma kininogen-deficient Brown Norway Katholiek rats was significantly lower than that in normal rats of the same strain, Brown Norway Kitasato rats.

  • These results indicate that BK released from low-molecular-weight kininogen by tissue kallikrein, but not from high-molecular-weight kininogen by plasma kallikrein, may be involved in the scratching behaviour induced by the injection of sodium deoxycholic acid in the rodent.

British Journal of Pharmacology (1999) 126, 197–204; doi:10.1038/sj.bjp.0702296

Ancillary