Pharmacological characterization of desensitization in scratching behavior induced by intrathecal administration of hemokinin-1 in the rat

Desensitization is induced by the repeated administration of high doses of substance P (SP) or hemokinin-1 (HK-1). However, little information is available about the mechanisms involved in the induction of desensitization by these peptides. Thus, to characterize this desensitization, we examined the dose-dependent effect of these peptides, the effect of pretreatment with neurokinin 1(NK1) receptor antagonists, and the effect of pretreatment with inhibitors of protein kinases such as protein kinase A (PKA), protein kinase C (PKC), calcium/calmodulin kinase II (CaMKII) and mitogen-activated protein kinase kinase (MEK). The number of scratchings induced by 10(-3) M SP or HK-1 decreased following pretreatment with 10(-11)-10(-3) M SP or HK-1 with a marked reduction at 10(-3) and 10(-6) M SP or HK-1. The effect of NK1 receptor antagonists on desensitization induced by pretreatment with 10(-6) M SP was marked, whereas there was little effect of pretreatment with these antagonists on 10(-6) M HK-1-induced desensitization. Additionally, 10(-6) M SP- and HK-1-induced desensitization was attenuated by pretreatment with PKA, PKC and MEK inhibitors, except a CaMKII inhibitor that inhibited SP-induced desensitization. These results indicate that the receptor and kinases involved in HK-1-induced desensitization are partially different from those of SP. (c) 2007 Elsevier Ltd. All rights reserved.