Role of L-type Ca 2+channels in attenuated morphine antinociception in streptozotocin-diabetic rats

• Published in: European journal of pharmacology Vol. 435; no. 2; pp. 187 - 194
• Main Authors: Gullapalli, Srinivas, Gurumoorthy, Krishnamoorthy, Kaul, Chaman Lal, Ramarao, Poduri
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2002
• Subjects: [ 3H]PN200-110; antinociception; Bmax; Morphine; Nimodipine; Saturation binding; Sterptozotocin-induced diabetes; Tail-flick; Sterptozotocin-induced diabetes; Tail-flick; antinociception; Nimodipine; B max; Saturation binding; [ 3H]PN200-110; Morphine
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)01593-X

The role of L-type Ca 2+ channels in morphine antinociception was studied in streptozotocin-induced diabetic and control rats, using [ 3H]PN200-110 {isopropyl 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-2,6-dimethyl-5-methoxycabonylpyridine-3-caboxylate} binding (0.005–1.0 nmol/l) and rat whole brain membranes, to determine if the attenuation of morphine antinociception was related to alterations in dihydropyridine-sensitive Ca 2+ channel binding characteristics. The tail-flick antinociceptive effect of morphine (4 mg/kg, i.p.) was significantly reduced in diabetic rats in comparison to that in controls. Nimodipine (0.1–3 mg/kg, i.p.) did not produce antinociception but significantly potentiated the morphine response in control rats. Nimodipine (0.3–3 mg/kg, i.p.) reversed the attenuation of morphine antinociception in a dose-dependent manner in diabetic rats. Moreover, insulin (2 μ/kg, s.c.) reversed the attenuated morphine antinociception in streptozotocin-diabetic rats. A significant increase in the B max (+41%) of [ 3H]PN200-110 binding was observed in diabetic rat brain membranes compared to that in control rats. However, there was no change in affinity ( K d) value of [ 3H]PN200-110. The reduced morphine response in diabetic rats, in accordance with up-regulation of dihydropyridine sites, may be due to an increased Ca 2+ influx through L-type channels. These results suggest a functional role of L-type Ca 2+ channels in morphine antinociception and the diabetic state may lead to alterations in their density.