KININ-INDUCED RELAXATIONS OF THE RAT DUODENUM

Both bradykinin (BK) and des-Arg9-BK induced relaxations of the isolated longitudinal smooth muscles of the rat duodenum. No contractile effects were observed with both peptides at concentrations up to 1-mu-mol/l. Des-Arg9-BK was about 1000 times less potent than BK. The novel B2 antagonist HOE 140 (D-Arg-[Hyp3, Thi5, D-Phe7, Oic8]-BK) potently inhibited the BK-induced relaxations, but did not affect the relaxations induced by des-Arg9-BK. Conversely, the B1 receptor antagonist des-Arg9-[Leu8]-BK only inhibited des-Arg9-BK, but did not affect BK-induced relaxations. The relaxations induced by BK and by des-Arg9-BK were inhibited by apamin (1-mu-mol/l) demonstrating that apamin-sensitive K+ channels are involved. In contrast, tetraethylammonium (1 mmol/l) did not inhibit the relaxations. BK-induced relaxations were reduced by about 25% in the presence of indomethacin (10-mu-mol/l) although the concentration-response curve to BK was not shifted to the left. Prostaglandin E1 caused relaxations with a pD2 value of 9.2. It is concluded that both BK and des-Arg9-BK can elicit relaxations of the rat duodenum via pharmacologically distinct kinin receptor subtypes, but via similar effector mechanisms.