Role of KATP channels in reduced antinociceptive effect of morphine in streptozotocin-induced diabetic mice.
The nociceptive effect was measured using withdrawal latency in tail flick test in mice rendered diabetic by administering streptozotocin (200 mg/kg, i.p.). The antinociceptive effect of morphine (4 and 8 mg/kg, s.c.) and cromakalim, a KATP channel opener, (0.3, 1 and 2 micrograms, i.c.v.) was significantly reduced in diabetic mice. Moreover, co-administration of cromakalim(0.3 microgram) did not alter the reduced antinociceptive effect of morphine(4 mg/kg) in diabetic mice. Spleenectomy in diabetic mice restored the decrease in antinociceptive effect of morphine and cromakalim. Multiple dose treatment with insulin to maintain euglycaemia for 3 days in diabetic mice prevented the decrease in antinociceptive effect of morphine and cromakalim. However, hyperglycaemic tyrode's buffer did not alter the pD2 value of morphine in isolated guinea pig ileum suggesting that hyperglycaemia does not interfere with mu receptor mediated responses in vitro. The results suggest that hyperglycaemia induced decrease in antinociceptive effect of morphine and cromakalim may be due to alteration in KATP channels. Some unknown factor from spleen in diabetic mice may be responsible for this alteration in KATP channels in diabetic mice.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
V
V
Sood
A
A
Sharma
M
M
Singh
D000255:Adenosine Triphosphate / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D019806:Cromakalim / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D013154:Spleen / Q000503:physiopathology
D000700:Analgesics; D015221:Potassium Channels; D019806:Cromakalim; D009020:Morphine; D000255:Adenosine Triphosphate