Role of NOC/oFQ in impaired opioid-induced pial artery dilation following brain injury.
Previous studies in piglets show that opioid-induced pial artery dilation was impaired following fluid percussion brain injury (FPI). This study was designed to determine the role of the newly described opioid nociceptin orphanin FQ (NOC/oFQ) in such impaired dilation to other opioids after FPI. CSF NOC/oFQ concentration was elevated from 70+/-6 to 444+/-56 pg/ml ( approximately 10(-10) M) within 1 h of FPI. Coadministration of NOC/oFQ (10(-10) M) with methionine enkephalin (10(-10), 10(-8), 10(-6) M) attenuated pial dilation induced by this opioid (7+/-1, 13+/-2, and 19+/-2 vs. 2+/-1, 6+/-1, and 7+/-2%) under non-brain injury conditions. Similar inhibition by NOC/oFQ was observed for leucine enkephalin and dynorphin. Methionine enkephalin (10(-10), 10(-8), 10(-6) M)-induced pial artery dilation was also inhibited within 1 h of FPI, but such responses were partially restored in animals pretreated with the NOC/oFQ receptor antagonist [F/G] NOC/oFQ (1-13) NH(2) (10(-6) M) (8+/-1, 14+/-1, and 21+/-1 vs. 1+/-1, 3+/-1, and 4+/-1 vs. 7+/-1, 11+/-1, and 17+/-1% for sham control, FPI and FPI pretreated with the NOC/oFQ receptor antagonist). Leucine enkephalin and dynorphin-induced pial artery dilation were similarly altered by FPI and partially restored by [F/G] NOC/oFQ (1-13) NH(2). These data indicate that the NOC/oFQ released by FPI contributes to impaired dilation to other opioids observed following this insult.
Armstead
W M
WM
Departments of Anesthesia and Pharmacology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA. armsteaw@mail.med.upenn.edu
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004399:Dynorphins / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D005260:Female; D008297:Male; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000134:cerebrospinal fluid* / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply; D013552:Swine; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D000097629:Nociceptin
D004399:Dynorphins; D004743:Enkephalin, Leucine; D004744:Enkephalin, Methionine; D018847:Opioid Peptides; D000097629:Nociceptin