Characterization of Ile,Ser-bradykinin-induced changes in short-circuit current across rat colon.
The effects of Ile,Ser-bradykinin (TK) on electrolyte secretion across mucosa of rat distal colon were determined and compared to those of bradykinin (BK). A segment of colon stripped of muscularis was mounted in an Ussing chamber for monitoring short-circuit current (Isc). Serosal application of TK and BK produced a concentration-dependent and transient increase in Isc with EC50(nM) values of 2.0 +/- 0.6 and 1.7 +/- 0.7, respectively. At a concentration of 1.0 microM, TK produced a maximal response of 130 +/- 18 compared to 75 +/- 13 microA/cm2 for BK. Increases in Isc induced by BK and TK were significantly (P less than .001) inhibited (90 +/- 4% for BK and 87 +/- 5% for TK) by serosal addition of bumetanide (10 microM). The lipoxygenase/cyclooxygenase inhibitor, eicosa-5,8,11,14-tetraynoic acid (0.1 mM), inhibited (P less than .01) the response to BK by 67 +/- 9% and to TK by 51 +/- 8%. Moreover, the cyclooxygenase inhibitor indomethacin (5.0 microM) significantly (P less than .05) inhibited the Isc response to 1.0 nM BK and 1.0 nM TK. Atropine (1.0 microM) did not block the effects of either kinin. Finally, the BK antagonist D-Arg0[Hyp3,Thi5,8,DPhe7]-bradykinin (2.0 microM) competitively antagonized the effect of BK and TK, shifting the concentration curve competitively to the right by 6-fold and 16-fold respectively. Another BK antagonist, [D-Phe7]-bradykinin (20 microM), also exhibited similar blockade effects. In this model, although some differences exist, BK and TK appear to act by the same mechanism, which may involve arachidonic acid metabolites.
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus.
X Y
XY
Tien
L J
LJ
Wallace
J F
JF
Kachur
S
S
Won-Kim
T S
TS
Gaginella
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D046508:Culture Techniques; D004594:Electrophysiology; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D002712:Chlorides; D007473:Ion Channels; D002034:Bumetanide; D013779:Tetrodotoxin; D001285:Atropine; C039065:T-kinin; D001920:Bradykinin