Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q13519 (OFQ)
 1,265 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to characterize the role of the newly described endogenous opioid nociceptin/orphanin FQ (NOC/oFQ) in reduced cerebral blood flow (CBF) observed after ischemia-reperfusion (I/R) and combined hypoxia and ischemia-reperfusion (H-I/R), as a function of time after onset of reperfusion in newborn pigs equipped with a closed cranial window. Global cerebral ischemia (20 min) was induced via elevation of intracranial pressure, whereas hypoxia (10 min) decreased PO(2) to 35 +/- 3 mmHg with unchanged PCO(2). I/R elevated cerebrospinal fluid (CSF) NOC/oFQ from 67 +/- 4 to 266 +/- 29 pg/ml within 1 h, whereas values returned to control level within 4 h of reperfusion. H-I/R elevated CSF NOC/oFQ to 483 +/- 67 pg/ml within 1 h, and such values returned slowly to control level within 12 h of reperfusion. Topical NOC/oFQ (10(-8) M, 10(-6) M)-induced vasodilation was attenuated by I/R and reversed to vasoconstriction by H-I/R at 1 h of reperfusion (control, 9 +/- 1 and 16 +/- 1%; I/R, 3 +/- 1 and 6 +/- 1%; H-I/R, -6 +/- 1 and -11 +/- 1%). Such altered dilation returned to control values within 4 h in I/R animals and within 12 h in H-I/R animals. Blood flow in the cerebrum was reduced from 58 +/- 4 to 33 +/- 2 ml x min(-1) x 100 g(-1) within 1 h and returned to control value within 4 h in I/R animals. In animals pretreated with [F/G]NOC/oFQ(1-13)-NH(2) (1 mg/kg iv), an NOC/oFQ antagonist, however, CBF only fell to 43 +/- 3 ml x min(-1) x 100 g(-1) at 1 h of reperfusion. Similar observations were made in H-I/R animals. These data suggest that an elevated CSF NOC/oFQ concentration and altered vascular responsiveness to this opioid contribute to reductions in CBF observed after either I/R or H-I/R.
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PMID:Relationship between nociceptin/orphanin FQ and cerebral hemodynamics after hypoxia-ischemia in piglets. 1066 78

This study was designed to determine if altered release of prostaglandins contributes to impaired pial artery dilation to the newly described opioid, nociceptin/orphanin FQ (NOC/oFQ), following hypoxia/ischemia in newborn pigs equipped with a closed cranial window. Global cerebral ischemia (20 min) was induced via elevation of intracranial pressure, while hypoxia (10 min) decreased P(O(2)) to 35+/-3 mmHg with unchanged P(CO(2)). NOC/oFQ (10(-8) and 10(-6) M) modestly increased cerebrospinal fluid (CSF) 6-Keto PGF(1alpha) and TXB(2), the stable breakdown products of PGI(2) and TXA(2), in sham animals (1199+/-39 to 1704+/-104 and 299+/-9 to 409+/-12 pg/ml for control and 10(-6) M NOC/oFQ 6-Keto PGF(1alpha) and TXB(2), respectively). In 1 h post ischemia/reperfusion (I+R) animals, basal levels of 6-Keto PGF(1alpha) and TXB(2) were elevated. NOC/oFQ-stimulated release of 6-Keto PGF(1alpha) was blocked while such release of TXB(2) was enhanced (526+/-15 to 822+/-36 pg/ml for control and 10(-6) M NOC/oFQ CSF TXB(2)). Similar, though more pronounced, changes were observed in hypoxia/ischemia/reperfusion (H+I+R) animals. Pretreatment with indomethacin (5 mg/kg i.v.) or SQ 29,548 (10(-4) M), cyclooxygenase and PGH(2)/TXA(2) receptor antagonists, partially restored attenuated NOC/oFQ pial artery dilation 1 h after I+R (9+/-1 and 18+/-1 vs. 3+/-1 and 6+/-1 vs. 8+/-1 and 13+/-1% for 10(-8) and 10(-6) M NOC/oFQ in sham, I+R, and I+R - SQ 29,548 pretreated animals). In contrast, NOC/oFQ-induced vasodilation was reversed to vasoconstriction in H+I+R animals and indomethacin or SQ 29,548 similarly partially restored such pial vasodilation. These data indicate that altered stimulated prostaglandin release contributes to hypoxic/ischemic impairment of NOC/oFQ-mediated pial artery dilation.
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PMID:Altered release of prostaglandins contributes to hypoxic/ischemic impairment of NOC/oFQ cerebrovasodilation. 1072 Jun 19

Previous studies in piglets show that either hypoxia, ischemia-reperfusion (I+R) or combined hypoxia-ischemia-reperfusion (H+I+R) attenuated N-methyl-D-aspartate (NMDA)-induced pial artery dilation. This study was designed to determine the contribution of the newly described opioid nociceptin orphanin FQ (NOC/oFQ) to hypoxic-ischemic impairment of NMDA induced cerebral vasodilation in piglets equipped with a closed cranial window. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia decreased P(O(2)) to 35+/-3 mmHg with unchanged P(CO(2)). I+R elevated CSF NOC/oFQ from 67+/-4 to 266+/-29 pg/ml ( approximately 10(-10) M) while H+I+R elevated CSF NOC/oFQ to 483+/-67 pg/ml within 1 h of reperfusion. Such elevated NOC/oFQ levels returned to control within 4 h in I+R animals and within 12 h in H+I+R animals. Topical NOC/oFQ (10(-10) M) had no effect on pial artery diameter by itself but attenuated NMDA (10(-8), 10(-6) M) induced pial dilation (control, 9+/-1 and 16+/-1; coadministered NOC/oFQ, 5+/-1 and 10+/-1%). NMDA induced pial artery dilation was attenuated by I+R or H+I+R; but such dilation was partially restored by pretreatment with the putative NOC/oFQ antagonist [F/G] NOC/oFQ (1-13) NH(2) (10(-6) M) (control, 9+/-1 and 16+/-1; I+R, 3+/-1 and 5+/-1; I+R+NOC/oFQ antagonist, 6+/-1 and 11+/-1%) Similar results were obtained for glutamate. These data suggest that NOC/oFQ release contributes to impaired NMDA and glutamate-induced cerebrovasodilation following I+R or H+I+R.
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PMID:NOC/oFQ contributes to hypoxic-ischemic impairment of N-methyl-D-aspartate-induced cerebral vasodilation. 1084 87

The effect of dynorphin A (Dyn A)-related peptides and nociceptin on the binding of the D2 receptor antagonist, [(3)H]raclopride, was examined in membrane preparations of rat heart. Non-linear regression saturation binding analysis of [(3)H]raclopride binding revealed the presence of a single high-affinity binding site with a K(d)of 4.1 n M and a B(max)of 220 fmol/mg protein. The D2 stereospecificity of [(3)H]raclopride binding was demonstrated by competition experiments using two enantiomer pairs of antagonists. (+)-Butaclamol (IC(50): 8.0 n M) and (-)-sulpiride (IC(50): 112.3 n M) were 27 000 and 24 times more potent than (-)-butaclamol (IC(50): >100 microm) and (+)-sulpiride (IC(50): 2666 n M), respectively. Nociceptin and Dyn A-(1-13) were also potent inhibitors of the binding of [3H]raclopride with shallow inhibition curves that fitted best with two sites model. Their order of potency on the low affinity site [alpha -Neo-endorphin>nociceptin>Dyn A-(2-13)>Dyn A-(1-13)>Dyn B>Dyn A-(6-10)] correlated well with their ability to inhibit the binding of [3H]nociceptin (r=0.82). The indirect nature of the inhibitory effects of the peptides on the D2 receptor was demonstrated by their inability to inhibit [(3)H]raclopride binding to a membrane preparation (Sf9 cells transfected with the human D2(long)receptor) that does not contain the ORL(1)receptor and the lack of effect of raclopride (0.1 n M-10 microm) on both [(3)H]nociceptin and [(3)H]Dyn A-(1-13) binding. Isolated cardiac mitochondrial-synaptosomal fractions submitted to ischemic conditions (1 m M iodoacetate +2 m M NaCN, 5 min at 37 degrees C) released 10.9% of their content in preloaded [(3)H]noradrenaline ([(3)H]NA). Dyn A-(1-13) (10 microm), nociceptin (10 microm) and the selective D2 receptor agonist, quinpirole (10 microm) were potent blockers of the release of [(3)H]NA evoked by the ischemic conditions. The inhibitory effect of Dyn A-(1-13), nociceptin and quinpirole were antagonized by the selective D2 receptor antagonist, raclopride (10 microm); whereas naloxone, at a concentration (1 microm) known to affect the ORL(1)receptor, blocked the effects of the peptides but not those of quinpirole. The results demonstrate the presence of D2 receptors in rat heart and suggest that Dyn A-(1-13) and nociceptin modulate ischemia-induced NA release by a mechanism that involves the participation of both ORL(1)and D2 receptors.
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PMID:Interactions of dynorphin A-(1-13) and nociceptin with cardiac D2 binding sites: inhibition of ischemia-evoked release of noradrenaline from synaptosomal-mitochondrial fractions. 1090 Jan 81

This study was designed to determine the role of altered cAMP and K(+) channel-dependent mechanisms in impaired pial artery dilation to the newly described opioid, nociceptin/orphanin FQ (NOC/oFQ) following hypoxia/ischemia in newborn pigs equipped with a closed cranial window. Recent studies have observed that NOC/oFQ elicits pial dilation via release of cAMP, which, in turn, activates the calcium sensitive (K(ca)) and the ATP-dependent K(+) (K(ATP)) channel. Global cerebral ischemia (20 min) was induced via elevation of intracranial pressure, while hypoxia (10 min) decreased pO(2) to 35+/-3 mm Hg with unchanged pCO(2). Topical NOC/oFQ (10(-8), 10(-6) M) induced vasodilation was attenuated by ischemia/reperfusion (I+R) and reversed to vasoconstriction by hypoxia/ischemia/reperfusion (H+I+R) at 1 h of reperfusion (control, 9+/-1 and 16+/-1%; I+R, 3+/-1 and 6+/-1%; H+I+R, -7+/-1 and -12+/-1%). Such altered dilation returned to control values within 4 h in I+R animals and within 12 h in H+I+R animals. NOC/oFQ dilation was associated with elevated CSF cAMP in control animals but such biochemical changes were attenuated in I+R animals and reversed to decreases in cAMP concentration in H+I+R animals (control, 1037+/-58 and 1919+/-209 fmol/ml; I+R, 1068+/-33 and 1289+/-30 fmol/ml; H+I+R, 976+/-36 and 772+/-27 fmol/ml for absence and presence of NOC/oFQ 10(-6) M, respectively). Topical 8-Bromo cAMP (10(-8), 10(-6) M) pial dilation was unchanged by I+R but blunted by H+I+R (control, 10+/-1 and 20+/-1%; I+R, 11+/-1 and 20+/-2%; H+I+R, 0+/-1 and 0+/-2%). Pituitary adenylate cyclase activating polypeptide and cromakalim, adenylate cyclase and K(ATP) channel activators, respectively, elicited dilation that was blunted by both I+R and H+I+R while NS1619, a K(ca) channel activator, elicited dilation that was unchanged by I+R but blunted by H+I+R. These data indicate that impaired NOC/oFQ dilation following I+R results form altered adenylate cyclase and K(ATP) channel-dependent mechanisms. These data further indicate that impaired NOC/oFQ dilation following H+I+R results not only from altered adenylate cyclase and K(ATP) channel but also from altered cAMP and K(ca) channel-dependent mechanisms.
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PMID:Role of cAMP and K(+) channel-dependent mechanisms in piglet hypoxic/ischemic impaired nociceptin/orphanin FQ-induced cerebrovasodilation. 1108 86

Previous studies in piglets show that hypercapnic pial artery dilation was blunted following cerebral ischemia. Unrelated studies show that the newly described opioid nociceptin orphanin FQ (NOC/oFQ) is released into cerebrospinal fluid and contributes to altered cerebral hemodynamics following hypoxia/ischemia. This study was designed to determine the contribution of NOC/oFQ to hypoxic/ischemic impairment of hypercapnic pial dilation in piglets equipped with a closed cranial window. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia decreased P(O2) to 34 +/- 3 mmHg. Topical NOC/oFQ (10(-10) M), the CSF concentration following hypoxia/ischemia, had no effect on pial artery diameter by itself but attenuated hypercapnia P(CO2) of (73 +/- 2 mmHg)-induced pial artery dilation (28 +/- 2 vs. 19 +/- 2%). Hypercapnia pial artery dilation was blunted by hypoxia/ischemia but such dilation was partially protected by pretreatment with the putative NOC/oFQ receptor antagonist, [F/G] NOC/oFQ (1-13) NH(2) (10(-6) M), (25 +/- 1, sham control; 4 +/- 1, hypoxia/ischemia; and 12 +/- 3%, hypoxia/ischemia + [F/G] NOC/oFQ (1-13) NH(2), respectively). These data suggest that NOC/oFQ release contributes to impaired hypercapnia-induced cerebrovasodilation following hypoxia/ischemia.
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PMID:Nociceptin/orphanin FQ contributes to hypoxic/ischemic impairment of hypercapnic cerebrovasodilation. 1154 45

Previous studies have observed that hypotensive pial artery dilation was blunted after hypoxia-ischemia. In unrelated studies, the opioid nociceptin/orphanin FQ (NOC/oFQ) was observed to contribute to hypoxic ischemic impairment of N-methyl-D-aspartate (NMDA)-induced pial dilation. This study determined the contribution of NOC/oFQ and NMDA to hypoxic ischemic hypotensive cerebrovasodilation impairment in newborn pigs equipped with a closed cranial window. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia decreased PO(2) to 33 +/- 3 mm Hg. Topical NOC/oFQ (10(-10) M), the cerebrospinal fluid concentration after hypoxia-ischemia, had no effect on pial artery diameter by itself but attenuated hypotension (mean arterial blood pressure decrease of 44 +/- 2%) -induced pial artery dilation (35 +/- 2% versus 22 +/- 3%). Hypotensive pial artery dilation was blunted by hypoxia-ischemia, but such dilation was partially protected by pretreatment with the putative NOC/oFQ receptor antagonist, [F/G] NOC/oFQ (1-13) NH(2) (10(-6) M; 29 +/- 2%, sham control; 7 +/- 2%, hypoxia-ischemia; and 13 +/- 2%, hypoxia-ischemia and [F/G] NOC/oFQ (1-13) NH(2)). Coadministration of the NMDA antagonist MK801 (10(-5) M) with NOC/oFQ(10(-10) M) partially prevented hypotensive pial dilation impairment. Similarly, pretreatment with MK801 partially protected hypoxic ischemia impairment of hypotensive pial dilation (35 +/- 2%, sham control; 7 +/- 1%, hypoxia-ischemia; 22 +/- 2%, hypoxia-ischemia + MK801). These data show that NOC/oFQ and NMDA contribute to hypoxic ischemic hypotensive cerebrovasodilation impairment. These data suggest that NOC/oFQ modulation of NMDA vascular activity also contributes to such hypotensive impairment.
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PMID:NOC/oFQ and NMDA contribute to piglet hypoxic ischemic hypotensive cerebrovasodilation impairment. 1197 81

Nociceptin is the endogenous ligand of the opioid OP4 or ORL1 (opioid receptor-like1) receptor. It decreases blood pressure and heart rate in anesthetized and conscious rats and mice after its intravenous and intracerebroventricular injection in a manner sensitive to OP4 but not to OP1-3 (or delta, kappa and mu opioid) receptor antagonists. OP4 receptors involved in the cardiovascular effects of nociceptin were identified on sensory afferent fibres, in brain areas including the nucleus tractus solitarii and the rostral ventrolateral medulla, on preganglionic and/or postganglionic sympathetic and parasympathetic nerve fibres innervating blood vessels and heart or directly on these target organs. These receptors do not seem to be tonically activated but may play a role in the pathophysiology of inflammation, arterial hypertension and cardiac or brain circulatory ischemia.
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PMID:Function of nociceptin and opioid OP4 receptors in the regulation of the cardiovascular system. 1236 30

This study characterized the contributions of protein tyrosine kinase (PTK) and mitogen-activated protein kinase (MAPK) in nociceptin/orphanin FQ (NOC/oFQ)-induced impairment of hypercapnic pial artery dilation (PAD) after hypoxia/ischemia (H/I) in piglets equipped with a closed cranial window. NOC/oFQ (10(-10) M cerebrospinal fluid H/I concentration) impaired hypercapnic PAD (21 +/- 2% vs. 13 +/- 1%). Coadministration of either of the PTK inhibitors genistein or tyrphostin A23 or the MAPK inhibitors U-0126 or PD-98059 with NOC/oFQ (10(-10) M) partially prevented the inhibition of hypercapnic PAD compared with that observed in their absence (21 +/- 2% vs. 17 +/- 1% for genistein). After exposure to H/I, PAD in response to hypercapnia was impaired, but pretreatment with either genistein, tyrphostin A23, U-0126, or PD-98059 partially protected such impairment (17 +/- 1% vs. 4 +/- 1% vs. 9 +/- 1% for sham control, H/I, and H/I + genistein pretreatment, respectively). These data show that PTK and MAPK activation contribute to NOC/oFQ-induced impairment of hypercapnic PAD. These data suggest that activation of PTK and MAPK is also involved in the mechanism by which NOC/oFQ impairs hypercapnic PAD after H/I.
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PMID:PTK, MAPK, and NOC/oFQ impair hypercapnic cerebrovasodilation after hypoxia/ischemia. 1248 17

Nociceptin/orphanin FQ is a newly described member of the opioid family. Previous minireviews in this series have described the contribution of important factors, including opioids, in the regulation of the cerebral circulation during physiologic and pathologic conditions. The present review extends these initial comments to an opioid whose vascular actions have only very recently been appreciated. In particular, this review discusses the contribution of nociceptin/orphanin FQ to impaired cerebral hemodynamics after cerebral hypoxia/ischemia and traumatic brain injury.
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PMID:Role of Nociceptin/Orphanin FQ in the physiologic and pathologic control of the cerebral circulation. 1248 5


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