Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Peptides. 2010 Aug;31(8):1613-6. doi: 10.1016/j.peptides.2010.04.025. Epub 2010 May 6.
Hemokinin-1 is a novel mammalian tachykinin cloned from mouse bone marrow. At present, pharmacological profile and physiological role of hemokinin-1 are still unclear. In the present study, we found that intrathecal (i.t.) administration of hemokinin-1 (0.00625-1.6 nmol) induced nociceptive responses consisting of scratching, biting and licking, which resemble substance P-induced behavioral responses in mice. The behaviors evoked by low-dose of hemokinin-1 (0.0125 nmol) were dose-dependently inhibited by i.t. co-administration of CP-99,994, a non-peptidic tachykinin NK(1) receptor antagonist, whereas high-dose of hemokinin-1 (0.1 nmol)-induced behaviors were not affected. Moreover, sendide, a peptidic tachykinin NK(1) receptor antagonist, failed to reduce the behavioral responses of both low- and high-dose of hemokinin-1. In contrast, substance P-induced behaviors were completely suppressed by both CP-99,994 and sendide. These results suggest that hemokinin-1 plays an important role in pain transmission at spinal cord. Moreover, the mechanism of hemokinin-1-induced nociceptive behaviors may be dose-dependent, and distinct from substance P-induced nociceptive behaviors.
血激肽-1 是一种从鼠骨髓中克隆出的新型哺乳动物速激肽。目前，血激肽-1 的药理学特征和生理作用尚不清楚。在本研究中，我们发现鞘内（i.t.）给予血激肽-1（0.00625-1.6 nmol）可引起类似于小鼠中 P 物质诱导的行为反应的疼痛反应，包括抓挠、咬和舔。低剂量（0.0125 nmol）的血激肽-1 诱发的行为可被鞘内共同给予 CP-99,994（非肽类速激肽 NK1 受体拮抗剂）剂量依赖性抑制，而高剂量（0.1 nmol）的血激肽-1 诱导的行为不受影响。此外，sendide（一种肽类速激肽 NK1 受体拮抗剂）不能减轻低剂量和高剂量血激肽-1 引起的行为反应。相比之下，CP-99,994 和 sendide 均可完全抑制 P 物质诱导的行为反应。这些结果表明，血激肽-1 在脊髓疼痛传递中起重要作用。此外，血激肽-1 诱导的疼痛行为的机制可能是剂量依赖性的，与 P 物质诱导的疼痛行为不同。
