Pharmacological characteristics of hemokinin-1-derived peptides in rat pruriceptive processing

Hemokinin-1 (HK-1) is a member of mammalian tachykinin peptide family, and [Leu¹¹]-HK-1 has an antagonistic effect on HK-1. The attenuation of pruritogen-induced scratching behavior by pretreatment with [Leu¹¹]-HK-1 indicates the involvement of HK-1 in pruriceptive processing. However, it remains unclear whether the intrathecal or intranasal administration of HK-1-derived peptides, such as [D-Trp^7,9]-[Leu¹¹]-HK-1 or [D-Trp⁷]-[Leu¹¹]-HK-1, elicits the effects different from [Leu¹¹]-HK-1. The induction of scratching by intrathecal administration of HK-1 was attenuated 30 min, 4 h and 24 h after pretreatment with [Leu¹¹]-HK-1, [D-Trp^7,9]-[Leu¹¹]-HK-1 and [D-Trp⁷]-[Leu¹¹]-HK-1 or [D-Trp⁹]-[Leu¹¹]-HK-1, respectively. Similarly, the scratching induced by subcutaneous injection of pruritogens as chloroquine and histamine was ameliorated 30 min and 24 h after pretreatment with [Leu¹¹]-HK-1 and these three HK-1-derived peptides, respectively. Moreover, the effective minimum concentrations of intrathecal administrations of [D-Trp⁹]-[Leu¹¹]-HK-1 on scratching induced by chloroquine and histamine were 10^-6 M, while the effective minimum concentrations of intranasal administration of this peptide on scratching induced by chloroquine and histamine were 10^-5 M and 10^-4 M, respectively. Thus, the present results indicate that the intrathecal administration of HK-1-derived peptides with D-Trp extends its effective time on scratching induced by intrathecal administration of HK-1 and pruritogens such as chloroquine and histamine. Similarly, the induction of scratching by pruritogens was attenuated by intranasal administration of HK-1-derived peptide, although the effective minimum concentration of this peptide was slightly lower than that of intrathecal administration, indicating that intranasal administration is an effective tool for carrying peptides into the brain.