Activation of a NO-cyclic GMP system by NO donors potentiates β-endorphin-induced antinociception in the mouse

Abstract

Nitric oxide (NO) donors such as sodium nitroprusside (SNP, 0.01-1 μg) or 3-morpholino-sydnonimine (SIN-1, 0.1–10 μg) administered intracerebroventricularly (i.c.v.) produced a dose-dependent potentiation of β-endorphin-induced antinociception assessed by the tail-flick test in ICR mice. The same i.c.v. treatment with SNP or SIN-1 did not affect the antinociception induced by μ-, δ-, or κ-opioid receptor agonists. The goal of the present study was to determine if the potentiation of the β-endorphin-induced antinociception by NO donors is mediated by the activation of a NO-cGMP system. Co-administration of hemoglobin (30–120 μg) or methylene blue (1.25-5 μg), but not N ω-nitro- l-arginine (1–5 μg) with β-endorphin (0.1 μg) given i.c.v. dose-dependently attenuated the potentiating effects of SNP or SIN-1 on β-endorphin-induced antinociception. However, the same i.c.v. treatments of mice with hemoglobin, methylene blue or N ω-nitro-L-arginine did not directly affect the i.c.v. administered β-endorphin-induced antinociception. On the other hand, the treatment of mice with a combination of NO donor (SNP, 0.1 μg or SIN-1, 1 μg) and zaprinast (a cGMP phosphodiesterase inhibitor, 1 μg) further potentiated β-endorphin-induced antinociception. These results indicate that the potentiating effect of SNP or SIN-1 on β-endorphin-induced antinociception is mediated by the increased production of NO-cyclic GMP in the brain. However, the NO-cGMP system is not directly involved in the β-endorphin-induced antinociception.