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.
Naono
R
R
Division of Neurobiology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan. rumi.n@fc.miyazaki-u.ac.jp
Nakayama
T
T
Ikeda
T
T
Matsusima
O
O
Nishimori
T
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003888:Desensitization, Immunologic; D007278:Injections, Spinal; D016014:Linear Models; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011537:Pruritus / Q000188:drug therapy* / Q000523:psychology*; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015320:Tachykinins / Q000008:administration & dosage / Q000494:pharmacology*
D064729:Neurokinin-1 Receptor Antagonists; D047428:Protein Kinase Inhibitors; D011812:Quinuclidines; D015320:Tachykinins; C507968:hemokinin-1; C076851:L 703606