The role of opioid receptors in hypoxic preconditioning against seizures in brain.
Preconditioning is defined as an adaptive mechanism produced by short periods of hypoxia/ischemia, resulting in protection against subsequent ischemic insult, and development of seizures. Results of the present study demonstrate that an episode of normobar hypoxia reduces the susceptibility to convulsions induced by pentylenetetrazol (PTZ) 30 min, 24 h, as well as 4 and 7 days later. Administration of morphine showed similar effects after 24 h. Naloxone, given before ischemic preconditioning, as well as morphine, blocked the development of the protection. Administration of D-Ala-Met-enkephalin-Gly-ol (DAMGO - a selective mu-opioid receptor agonist), as well as trans-3, 4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl) cycloexilbenzeneacetamide ethane sulfonate] (U-69,593 - a selective kappa-opioid receptor agonist), mimicked the effects of hypoxic preconditioning (HPC). (-)-N-(Cyclopropylmethyl)-4,14-dimethoxymorphinan-6-one (cyprodime - a selective mu-opioid receptor antagonist, as well as nor-binaltorphimine dihydrochloride (nor-BNI - selective kappa-opioid receptors antagonist), given before HPC as well as before respective opioid receptor agonists, blocked the development of the protection. This study provides evidence that mu- and kappa-opioid receptors are involved in HPC against seizures in the brain.
Rubaj
A
A
Department of Pharmacology, Lublin Medical University, Jaczewskiego 8, 20-090, Lublin, Poland.
Gustaw
K
K
Zgodziński
W
W
Kleinrok
Z
Z
Sieklucka-Dziuba
M
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D011957:Receptors, Opioid / Q000502:physiology*; D012640:Seizures / Q000517:prevention & control*
D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D009020:Morphine