Effects of dynorphin1-13 on opiate binding and dopamine and GABA uptake in stroked cat brain.
We previously reported that the opioid peptide dynorphin1-13 improves survival chances in stroked cats. Some evidence also suggests that changes in dopamine and gamma-aminobutyric acid (GABA) uptake may be associated with stroke. In the present study, therefore, we determined binding of the opiate [3H]ethylketocyclazocine (EKC), as well as dopamine and GABA uptake in various brain regions of control, stroked and dynorphin1-13-treated stroked cats. Cats were stroked by middle cerebral artery occlusion. In the EKC binding study, the Kd of the high-affinity site of the occluded cortex was significantly increased, relative to that of both the unoccluded side and control cortex. Dynorphin1-13 treatment reversed this effect, lowering the Kd to control level. In the dopamine uptake study, the Km was decreased and Vmax was increased significantly in unoccluded cortex, compared with that in the occluded cortex or in control cortex. Again, dynorphin1-13 reversed these effects, raising the Km and lowering the Vmax. However, the Km of occluded cortex was also increased so that it became significantly higher than that of control cortex. The Km of unoccluded subcortex in stroked cats treated with dynorphin1-13 was significantly reduced compared with control. In the GABA uptake study, there was no significant change in any parameter. The change in opioid binding observed here and its reversal by dynorphin1-13 are consistent with the notion that the peptide's beneficial effect on stroke is mediated through opiate receptors. Since opioid systems in the brain are known to have association with dopaminergic ones, the change in dopamine uptake could also be the result of an opioid effect.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002415:Cats; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004399:Dynorphins / Q000494:pharmacology*; D016314:Ethylketocyclazocine; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000032:analysis / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D010446:Peptide Fragments; D011957:Receptors, Opioid; D005680:gamma-Aminobutyric Acid; D016314:Ethylketocyclazocine; C026843:dynorphin (1-13); D004399:Dynorphins; D003496:Cyclazocine; D004298:Dopamine