Pharmacological profile of the novel mammalian tachykinin, hemokinin 1статья из журнала
Аннотация: 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
Год издания: 2002
Авторы: Francesca Bellucci, Francesca Maria Carini, Claudio Catalani, Paola Cucchi, Alessandro Lecci, Stefania Meini, Riccardo Patacchini, Laura Quartara, Renzo Ricci, Manuela Tramontana, Sandro Giuliani, Carlo Alberto Maggi
Издательство: Wiley
Источник: British Journal of Pharmacology
Ключевые слова: Neuropeptides and Animal Physiology, Receptor Mechanisms and Signaling, Pharmacological Effects and Assays
Другие ссылки: British Journal of Pharmacology (HTML)
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Том: 135
Выпуск: 1
Страницы: 266–274