RECEPTORS FOR KININS IN THE HUMAN ISOLATED UMBILICAL VEIN

1 The human umbilical vein has been found to contract in response to b radykinin (BK) and desArg(9)BK. 2 The rank order of potency of agonist s, in the presence of the B-1 receptor antagonist Lys[Leu(8)]desArg(9) BK, is as follows: [Hyp(3),Tyr(Me)(8)]BK (pD(2) 8.88)=[Hyp(3)]BK (pD(2 ) 8.86)=LysBK (pD(2) 8.81) greater than or equal to BK (pD(2) 8.60) mu ch greater than [Aib(7)]BK (pD(2) 6.38) much greater than desArg(9)BK and LysdesArg(9)BK (inactive). 3 Hoe 140 (pA(2) 8.42) inhibits the eff ects of BK while other B-2 receptor peptide antagonists are very weak and WIN 64338 is practically inactive. 4 Venoconstrictor responses to desArg(9)BK of fresh tissues increase with time during the in vitro in cubation and reach a maximum after 4-6 h. The activity of Hoe 140 (pA( 2) 5.48) is negligible against B-1 receptor agonists. 5 When measured in the presence of the selective B-2 receptor antagonist Hoe 140 (400 nM), the order of potency of kinin related peptides on the B-1 recepto r is Lys[desArg(9)]BK (pD(2) 8.60) > desArg(9)BK (pD(2) 6.69). BK, Lys BK, [Hyp(3)]BK and other B-2 receptor agonists are inactive. 6 The B-1 receptor antagonist, Lys[Leu(8)]desArg(9)BK (pA(2) 7.99), inhibits th e response of the human vein to B-1 receptor agonists (LysdesArg(9)BK or desArg(9)BK), but do not alter the effect of BK. 7 The results summ arized in this paper indicate that the human isolated umbilical vein i s a sensitive preparation containing both B-1 and B-2 receptors. The h uman B-2 receptor shows some similarity with that of the rabbit (at le ast for agonist potencies) and differs from the B-2 receptor of the gu inea-pig. Compared to the rabbit B-1 receptor, the human B-1 receptor shows low sensitivity to peptides that lack the N-terminal Lys.