Possible involvement of protein kinase C in the attenuation of [D-Ala2, NMePhe4, Gly-ol5]enkephalin-induced antinociception in diabetic mice.
The effects of pretreatment with a highly selective protein kinase C inhibitor, calphostin C, on the antinociception induced by the intracerebroventricular (i.c.v.) administration of the mu-opioid receptor agonist [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO) were studied in diabetic and non-diabetic mice. The antinociceptive potency of i.c.v. DAMGO in diabetic mice was lower than that in non-diabetic mice. I.c.v. pretreatment with phorbol 12,13-dibutyrate (50 pmol), a protein kinase C activator, for 60 min attenuated the antinociception induced by i.c.v. DAMGO in non-diabetic mice, but not in diabetic mice. I.c.v. pretreatment with calphostin C (3 pmol) for 60, 120 and 240 min, but not 10 min, increased the antinociceptive effect of DAMGO (10 ng) in diabetic mice, but not in non-diabetic mice. The dose-response curve for DAMGO-induced antinociception in diabetic mice, but not in non-diabetic mice, was shifted to the left by i.c.v. pretreatment with calphostin C (3 pmol) for 60 min. In non-diabetic mice, i.c.v. pretreatment with a high dose of calphostin C (10 pmol) for 60 and 120 min potentiated DAMGO-induced antinociception. These results indicate that protein kinase C may be involved in DAMGO-induced antinociception in mice. Furthermore, these results suggest that the attenuation of DAMGO-induced antinociception in diabetic mice may be due in part to increased protein kinase C activity.
Ohsawa
M
M
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Kamei
J
J
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009281:Naphthalenes / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D012016:Reference Values
D000701:Analgesics, Opioid; D004745:Enkephalins; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; C058819:calphostin C