Wiesenfeld-Hallin Z, Luo L, Xu X J, Maggi C A
Department of Laboratory Medical Science and Technology, Huddinge University Hospital, Karolinska Institute, Sweden.
Eur J Pharmacol. 1994 Jan 4;251(1):99-102. doi: 10.1016/0014-2999(94)90449-9.
The effects of intrathecally (i.t.) injected selective tachykinin NK2 receptor antagonists, MEN 10,207, MEN 10,376 and R396, on the spinal effect of neurokinin A were studied in decerebrate, spinalized, unanesthetized rats. I.t. neurokinin A (7 pmol) briefly facilitated the flexor reflex, an effect that was dose dependently inhibited by pretreatment with MEN 10,207 and MEN 10,376 with similar and high potency. I.t. R396 itself caused strong facilitation of the flexor reflect. At lower doses, the effect of i.t. neurokinin A was potentiated by R396. R396 only exhibited moderate antagonism of neurokinin A-induced reflex facilitation even at very high doses. It has been proposed that the tachykinin NK2 receptor may be further classified into two subtypes, NK2A and NK2B, with MEN 10,207 and MEN 10,376 having high affinity for the former and R396 for the latter. Our results suggested that the tachykinin NK2 receptor in rat spinal cord which mediates the excitatory effect of neurokinin A may belong to the NK2A subpopulation of receptors.
在去大脑、脊髓横断、未麻醉的大鼠中，研究了鞘内注射选择性速激肽NK2受体拮抗剂MEN 10,207、MEN 10,376和R396对神经激肽A脊髓效应的影响。鞘内注射神经激肽A（7皮摩尔）可短暂促进屈肌反射，MEN 10,207和MEN 10,376预处理可剂量依赖性地抑制该效应，且二者效力相似且较高。鞘内注射R396本身可强烈促进屈肌反射。在较低剂量时，R396可增强鞘内注射神经激肽A的效应。即使在非常高的剂量下，R396对神经激肽A诱导的反射促进作用仅表现出中等程度的拮抗作用。有人提出，速激肽NK2受体可能进一步分为两种亚型，即NK2A和NK2B，MEN 10,207和MEN 10,376对前者具有高亲和力，而R396对后者具有高亲和力。我们的结果表明，介导神经激肽A兴奋作用的大鼠脊髓速激肽NK2受体可能属于受体的NK2A亚群。
