Pharmacological profile of the novel mammalian tachykinin, hemokinin 1

1 The effects of the novel mammalian tachykinin, hemokinin 1 (HEK-1), have been investigated by radioligand binding and functional in vitro and in giro experiments. 2 Similar to SP (K-t=0.13 nM), HEK-1 inhibited in a concentration-dependent manner and with high affinity [H-3]-substance P (SP) binding to human NK1 receptor (K-t=0.175 nM) while its affinity for [I-125]-neurokinin A (NKA) binding at human NK2 receptor was markedly lower (K-t-560 nm). 3 In isolated bioassays HEK-1 was a full agonist at tachykinin NK1, NK2 and NK3 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 affinities comparable to that measured against tachykinin NK1, NK2 and NK3 receptor-selective agonists, respectively. 5 Intravenous HEK-1 produced dose-related decrease of blood pressure in anaesthetized guinea-pigs (ED50 = 0.1 nmol kg (1)) and salivary secretion in anaesthetized rats (ED50 = 6 nmol kg (1)) with potencies similar to that of SP. All these effects were blocked by the selective tachykinin NK1 receptor antagonist. SR 140333. 6 We conclude that HEK-1 is a full agonist at tachykinin NK1, NK2 and NK3 receptors, possesses a remarkable selectivity for NK1 as compared to NK2 or NK3 receptors and acts in vivo experiments with potency similar to that of SP.