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Pharmacological profile of the novel mammalian tachykinin, hemokinin 1
Author(s) -
Bellucci Francesca,
Carini Francesca,
Catalani Claudio,
Cucchi Paola,
Lecci Alessandro,
Meini Stefania,
Patacchini Riccardo,
Quartara Laura,
Ricci Renzo,
Tramontana Manuela,
Giuliani Sandro,
Maggi Carlo Alberto
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704443
Subject(s) - tachykinin receptor , hek 293 cells , neurokinin b , agonist , neurokinin a , receptor , substance p , chemistry , medicine , endocrinology , in vivo , pharmacology , biology , neuropeptide , biochemistry , microbiology and biotechnology
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 ( K i =0.13 nM), HEK‐1 inhibited in a concentration‐dependent manner and with high affinity [ 3 H]‐substance P (SP) binding to human NK 1 receptor ( K i =0.175 n M ) while its affinity for [ 125 I]‐neurokinin A (NKA) binding at human NK 2 receptor was markedly lower ( K i =560 n M ). 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. 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 NK 1 , NK 2 and NK 3 receptor‐selective agonists, respectively. Intravenous HEK‐1 produced dose‐related decrease of blood pressure in anaesthetized guinea‐pigs (ED 50 =0.1 nmol kg −1 ) and salivary secretion in anaesthetized rats (ED 50 =6 nmol kg −1 ) with potencies similar to that of SP. All these effects were blocked by the selective tachykinin NK 1 receptor antagonist, SR 140333. 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.British Journal of Pharmacology (2002) 135 , 266–274; doi: 10.1038/sj.bjp.0704443