Abstract
To test our hypothesis that the abnormally low efficacy of μ-opioid agonists in diabetic mice may be due to functional changes in ATP-sensitive potassium channels, we evaluated the effects of cromakalim on the tail-flick latencies in diabetic and non-diabetic mice. Anti nociceptive effects of morphine (10 µg, ICV) in diabetic mice were significantly less than that in non-diabetic mice. Morphine-induced antinociception in non-diabetic mice was antagonized by pretreatment with glibenclamide (30 µg, ICV), an ATP-sensitive potassium channel blocker. Cromakalim (0.3 and 1 µg, ICV) produced significant, dose-dependent antinociception in non-diabetic mice, which was significantly reduced by pretreatment with glibenclamide. However, cromakalim did not markedly affect the tail-flick latencies in diabetic mice, even at higher doses (3 µg, ICV). On the other hand, [D-Pen2,5]enkephaline (DPDPE, 5 µg, ICV), a selective δ-opioid receptor agonist, produced significant antinociception in both diabetic and non-diabetic mice. Since pretreatment with glibenclamide significantly reduced the antinociceptive effect of DPDPE in non-diabetic mice but not in diabetic mice, δ-opioid receptor-mediated antinociception in diabetic mice may be independent of potassium channels. These results suggest that dysfunction of ATP-sensitive potassium channels may contribute to the demonstrated poor antinociceptive response of diabetic mice to μ-opioid agonists.
Similar content being viewed by others
References
Amoroso S, Schmid-Antomarchi H, Fosset M, Lazdunski M (1990) Glucose, sulfonylureas, and neurotransmitter release: role of ATP-sensitive K+ channels, Science 247:852–854
Brase DA, Han TH, Dewey WL (1987) Effects of glucose and diabetes on binding of naloxone and dihydromorphine to opiate receptors in mouse brain. Diabetes 36:1173–1177
Cook DL, Hales N (1984) Intracellular ATP directly blocks K+ channels in pancreatic β-cells. Nature 311:271–273
Cook NS (1988) The pharmacology of potassium channels and their therapeutic potential. TIPS 9:21–28
D'Amour WL, Smith DL (1941) A method for determining loss of pain sensation. J Pharmacol Exp Ther 72:74–79
Dewey WL, Harris LS, Howes JF, Nuite JA (1970) The effect of various neurochemical modulators on the activity of morphine and the narcotic antagonists in the tail-flick and phenylquinone tests. J. Pharmacol Exp Ther 175:435–442
Findlay I, Dunne MJ, Peterson OH (1985) ATP-sensitive inward rectifier and voltage- and calcium-activated K+ channels in cultured pancreatic islet calls. J Membr Biol 88:165–172
Fosset M, De Weeille JR, Green RD, Schmid-Antomarchi H, Lazdunski M (1988) Antidiabetic sulfonylureas control action potential properties in heart cells via high affinity receptors that linked to ATP-dependent K+ channels, J Biol Chem 263:7933–7936
Haley TJ, McCormick WG (1957) Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br J Pharmacol 12:12–15
Kakei M, Nama A, Shibasaki T (1985) Properties of adenosinetriphosphate-regulated potassium channels in guinea-pig ventricular cells. J Physiol 363:441–462
Kamei J, Kawashima N, Kasuya Y (1992a) Role of spleen or spleen products in the deficiency in morphine-induced analgesia in diabetic mice. Brain Res 576:139–142
Kamei J, Ohhashi Y, Aoki, T, Kawashima N, Kasuya Y (1992b) Streptozotocin-induced diabetes selectively alters the potency of analgesia produced by μ-opioid agonists, but not by δ- and κ-opioid agonists. Brain Res 571:199–203
Kamei J, Kawashima N, Kasuya Y (1993) Serum glucose level-dependent and independent modulation of μ-opioid agonist-mediated analgesia in diabetic mice. Life Sci 52:53–60
Narita M, Takamori K, Kawashima N, Funada M, Kamei J, Suzuki T, Misawa M, Nagase H (1993) Activation of central ATP-sensitive potassium channels produces the antinociception and spinal noradrenaline turnover-enhancing effect in mice. Psychopharmacology (in press)
Noma A (1983) ATP-regulated K+ channels in cardiac muscle. Nature 305:147–148
Ocana M, Pozo ED, Barrios M, Robles LI, Baeyens JM (1990) An ATP-dependent potassium channel blocker antagonizes morphine analgesia. Eur J Pharmacol 186:377–378
Petersen OH, Findlay I (1987) Electrophysiology of the pancreas. Physiol Rev 67:1054–1116
Singh IS, Chaterjee TK, Ghosh JJ (1983) Modification of morphine antinociceptive response by blood glucose status: possible involvement of cellular energetics. Eur J Pharmacol 90:437–439
Spruce AE, Standen NB, Stanfield PR (1985) Voltage-dependent ATP-sensitive potassium channels of skeletal muscle membrane. Nature 316:736–738
Standen NB, Quayle JM, Davies NW, Brayden JE, Huang Y, Nelson MT (1989) Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science 245:177–180
Stanfield PR (1987) Nucleotides such as ATP may control the activity of ion channels. TINS 10:335–339
Werz MA, MacDonald RL (1983) Opioid peptides selective for μ-and δ-opate receptors reduce calcium-dependent action potential duration by increasing potassium conductance. Neurosci Lett 42:173–178
Werz MA, MacDonold RL (1985) Dynorphin and neoendorphin peptides decrease dorsal root ganglion neuron calcium-dependent action potential duration. J Pharmacol Exp Ther 234:49–56
Wild KD, Vanderah T, Mosberg HI, Porreca F (1991) Opioid δ receptor subtypes are associated with different potassium channels. Eur J Pharmacol 193:135–136
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kamei, J., Kawashima, N., Narita, M. et al. Reduction in ATP-sensitive potassium channel-mediated antinociception in diabetic mice. Psychopharmacology 113, 318–321 (1994). https://doi.org/10.1007/BF02245203
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245203