Intraventricular insulin reduces the antinociceptive effect of [d-Ala², NMePhe⁴, Gly-ol⁵]enkephalin in mice

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• 作者：Kamei ; Junzo ; Ohsawa ; Masahiro ; Sodeyama ; Midori ; Kimura ; Mari ; Tanaka ; Shyun-ichi
• 关键词：Antinociception ; μ ; -Opioid receptor ; Protein tyrosine kinase ; Lavendustin A ; Protein kinase C ; C57BL/KsJ-db/db mice ; Diabetes
• 刊名：European Journal of Pharmacology
• 出版年：1998
• 出版时间：March 19, 1998
• 年：1998
• 卷：345
• 期：2
• 页码：171-174
• 全文大小：315 K

文摘

The effects of pretreatment with insulin on the antinociception induced by intracerebroventricular (i.c.v.) administration of the μ-opioid receptor agonist [-Ala², NMePhe⁴, Gly-ol⁵]enkephalin (DAMGO) were studied in mice. Intracerebroventricular pretreatment with insulin (1 and 3 mU) for 60 min dose dependently attenuated the antinociception induced by i.c.v. DAMGO (5.6 ng) in mice. Intracerebroventricular pretreatment with a highly selective tyrosine kinase inhibitor, lavendustin A, at doses of 100 and 300 ng for 10 min, dose dependently reversed the antinociceptive effect of DAMGO (5.6 ng) in insulin-treated mice. The antinociceptive effect of DAMGO (5.6 ng, i.c.v.) was significantly reduced in C57BL/KsJ-db/db diabetic mice compared with that in age-matched control (C57BL/KsJ-db/++) mice. When C57BL/KsJ-db/db diabetic mice were pretreated with lavendustin A (300 ng), the antinociceptive effect of DAMGO was significantly increased. These results indicate that tyrosine kinase may be involved in the reduction of DAMGO-induced antinociception by insulin in mice. Furthermore, the attenuation of DAMGO-induced antinociception in C57BL/KsJ-db/db diabetic mice may be due in part to increased tyrosine kinase activity as a result of hyperinsulinemia.