Expression of Bradykinin Receptors and Effects of Bradykinin in the Interstitial Cells of Cajal from Mouse Small Intestine / 체질인류학회지

Interstitial Cells of Cajal (ICC) are pacemaker cells that generates slow waves and drive spontaneous mechanical contractions of gastrointestinal smooth muscle. Slow waves are generated the periodic activation of spontaneous inward currents (pacemaker currents). We studied the modulation of pacemaker activities by bradykinin (10-8 M) in cultured ICC with the whole cell patch-clamp technique, and the localization of bradykinin-2 receptor-immunoreactivity using double labelling immunohistochemistry in the murine small intestine. Externally applied bradykinin produced membrane depolarization in current-clamping mode. At a -70 mV of holding potential bradykinin increased tonic inward pacemaker currents. Double labelling with bradykinin-2 receptor and and c-kit was shown that ICC expressed the bradykinin-2 receptor-immunoreactivity. These results suggest that bradykinin modulates electrical activities of ICC via bradykinin-2 receptor, which may regulate gastrointestinal motility.

Role of Tyrosine Kinases in Norepinephrine-Induced Vascular Contraction in Renal Hypertensive Rats

BACKGROUND AND OBJECTIVES: Protein tyrosine kinases appear to be involved in the signal transduction mechanisms, which result in vascular smooth muscle contraction, as well those required in cell growth. The present study was conducted to examine the role of tyrosine kinases in the norepinephrine-induced vascular smooth muscle contraction of isolated aortae from two-kidney, one clip (2K1C) hypertensive rats. MATERIALS AND METHODS: 2K1C hypertension was made by clipping the left renal artery of the rats, with age-matched rats receiving a sham treatment serving as controls. Thoracic aortae denuded of endothelium were mounted in tissue baths to measure the isometric tension. RESULTS: The putative tyrosine kinase inhibitors, genistein and tyrphostin 25, significantly inhibited the contractile responses of the aorta to norepinephrine in the control rats, but not in the 2K1C rats. The protein tyrosine phosphatase inhibitor, sodium orthovanadate, selectively potentiated the contractile response to norepinephrine, but only in the controls. Genistein, tyrphostin 25 and sodium orthovanadate did not affect KCl-induced vascular contractions in either the 2K1C or the controls. The vascular contraction elicited by phorbol 12, 13 dibutyrate, in the presence and absence of genistein, did not alter in either the 2K1C or the controls. CONCLUSION: These findings indicate that protein tyrosine kinases participate in the norepinephrine-induced contraction of rat aortic smooth muscle, where the role is attenuated in 2K1C renal hypertension.