Pharmacological profile of the novel mammalian tachykinin, hemokinin 1

The effects of the novel mammalian tachykinin, hemokinin 1 (HEK‐1), have been investigated by radioligand binding and functional in vitro and in vivo experiments. Similar to SP (Ki=0.13 nM), HEK‐1 inhibited in a concentration‐dependent manner and with high affinity [3H]‐substance P (SP) binding to human NK1 receptor (Ki=0.175 nM) while its affinity for [125I]‐neurokinin A (NKA) binding at human NK2 receptor was markedly lower (Ki=560 nM). 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. The responses to HEK‐1 were antagonized by GR 82334 in RUB (pKB=5.6±0.07), by nepadutant in RPA (pKB=8.6±0.04) and by SR 142801 in GPI (pKB=9.0±0.2) with apparent affinities comparable to that measured against tachykinin NK1, NK2 and NK3 receptor‐selective agonists, respectively. 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. 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. British Journal of Pharmacology (2002) 135, 266–274; doi:10.1038/sj.bjp.0704443