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

Abstract:

: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.

journal_name

Neuropeptides

journal_title

Neuropeptides

authors

Naono R,Nakayama T,Ikeda T,Matsusima O,Nishimori T

doi

10.1016/j.npep.2007.10.004

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

47-55

issue

1

eissn

0143-4179

issn

1532-2785

pii

S0143-4179(07)00098-4

journal_volume

42

pub_type

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