Intraventricular insulin reduces the antinociceptive effect of [D-Ala2, NMePhe4, Gly-ol5]enkephalin in mice.
The effects of pretreatment with insulin on the antinociception induced by intracerebroventricular (i.c.v.) administration of the mu-opioid receptor agonist [D-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.
Kamei
J
J
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Science, Hoshi University, Tokyo, Japan. kamei@hoshi.ac.jp
Ohsawa
M
M
Sodeyama
M
M
Kimura
M
M
Tanaka
S
S
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007276:Injections, Intraventricular; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017288:Pain Threshold / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000502:physiology
D000701:Analgesics, Opioid; D004745:Enkephalins; D004791:Enzyme Inhibitors; D007328:Insulin; D010636:Phenols; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C062898:lavendustin A; D011505:Protein-Tyrosine Kinases