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1 The e ects of the novel mammalian tachykinin, hemokinin 1 (HEK-1), have been investigated by radioligand binding and functional in vitro and in vivo experiments. 2 Similar to SP (K i =0.13 nM), HEK-1 inhibited in a concentration-dependent manner and with high a nity [ 3 H]-substance P (SP) binding to human NK 1 receptor (K i =0.175 nM) while its a nity for [ 125 I]-neurokinin A (NKA) binding at human NK 2 receptor was markedly lower (K i =560 nM). 3 In isolated bioassays HEK-1 was a full agonist at tachykinin NK 1 , NK 2 and NK 3 receptors. In the rat urinary bladder (RUB) HEK-1 was about 3 fold less potent than SP. In the rabbit pulmonary artery (RPA) HEK-1 and in the guinea-pig ileum (GPI), HEK-1 was about 500 fold less potent than NKA and NKB, respectively. 4 The responses to HEK-1 were antagonized by GR 82334 in RUB (pK B =5.6+0.07), by nepadutant in RPA (pK B =8.6+0.04) and by SR 142801 in GPI (pK B =9.0+0.2) with apparent a nities comparable to that measured against tachykinin NK 1 , NK 2 and NK 3 receptor-selective agonists, respectively. 5 Intravenous HEK-1 produced dose-related decrease of blood pressure in anaesthetized guineapigs (ED 50 =0.1 nmol kg 71 ) and salivary secretion in anaesthetized rats (ED 50 =6 nmol kg 71 ) with potencies similar to that of SP. All these e ects were blocked by the selective tachykinin NK 1 receptor antagonist, SR 140333. 6 We conclude that HEK-1 is a full agonist at tachykinin NK 1 , NK 2 and NK 3 receptors, possesses a remarkable selectivity for NK 1 as compared to NK 2 or NK 3 receptors and acts in vivo experiments with potency similar to that of SP.

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