RT Journal Article
SR Electronic
T1 Role of Intracellular Calcium in Modification of<em>Mu</em> and <em>Delta</em> Opioid Receptor-Mediated Antinociception by Diabetes in Mice
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 780
OP 787
VO 286
IS 2
A1 Masahiro Ohsawa
A1 Hiroshi Nagase
A1 Junzo Kamei
YR 1998
UL http://jpet.aspetjournals.org/content/286/2/780.abstract
AB We examined the effects of calcium modulators on mu anddelta opioid receptor agonist-induced antinociception in both diabetic and nondiabetic mice. In nondiabetic mice, intracerebroventricular (i.c.v.) pretreatment with calcium and thapsigargin, which increase intracellular calcium, reduced [d-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO)-induced antinociception by shifting its dose-response curve to the right. However, in diabetic mice i.c.v. pretreatment with calcium and thapsigargin did not affect DAMGO-induced antinociception. In contrast i.c.v. administration of agents that decrease intracellular calcium, such as EGTA and ryanodine, enhanced DAMGO-induced antinociception in both diabetic and nondiabetic mice. In contrast with DAMGO i.c.v. pretreatment with calcium and thapsigargin enhanced (−)-TAN67-induced antinociception in nondiabetic mice by shifting its dose-response curve to the left. However, (−)-TAN67-induced antinociception in diabetic mice was not affected by pretreatment with calcium or thapsigargin. Moreover i.c.v. pretreatment with EGTA, but not with ryanodine, reduced (−)-TAN67-induced antinociception in nondiabetic mice. In diabetic mice i.c.v. pretreatment with both EGTA and ryanodine reduced (−)-TAN67-induced antinociception. These results suggest that cytosolic calcium has different effects onmu and delta opioid receptor agonist-induced antinociception. Further, these results suggest that the modification of mu and delta opioid receptor agonist-induced antinociception by diabetes in mice may be due to increased levels of intracellular calcium. The American Society for Pharmacology and Experimental Therapeutics