Nociceptin/Orphanin FQ Content is Decreased in Forebrain Neurones During Acute Stress

We examined the effects of acute and chronic stress on neurotransmission of nociceptin/orphanin FQ (N/OFQ) in a variety of brain regions. Four groups of rats were exposed to chronic variable stress, and/or a single acute stress before decapitation. Group 1 served as unstressed controls. The rats in group 2 (chronic stress/no acute stress) were exposed to a 10-day regimen of chronic stress (two unpredictable stressors per day). These rats were decapitated 20 h after the last stressor. The rats in group 3 (no chronic stress/acute stress) were not exposed to chronic stress, but they were restrained for 30 min prior to decapitation. The rats in group 4 (chronic stress/acute stress) were chronically stressed for 10 days, and were then restrained prior to decapitation. Trunk blood was collected, and plasma adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) were assayed by radioimmunoassay (RIA). The rats' brains were dissected, and N/OFQ content was measured by RIA in a variety of brain regions, and in spinal cord. Chronic stress exposure altered the hormonal responses to the acute stress exposure. In the rats that were exposed to chronic stress without acute stress (group 2), N/OFQ content did not differ from the content of the unstressed controls in any of the dissected brain regions. In the two groups that were stressed acutely just before decapitation (groups 3 and 4), N/OFQ content was decreased by 25–30% in the basal forebrain. Accordingly, the neuronal content of N/OFQ is decreased in basal forebrain neurones during acute stress exposure. In light of our previous finding that N/OFQ administration increases circulating ACTH and CORT concentrations, and augments hormonal responses to an acute stressor, the current finding raises the possibility that endogenous N/OFQ participates in neuronal regulation of hormonal responses to acute stress exposure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73048/1/j.1365-2826.2003.00868.x.pd

Molecular basis for dynorphin A selectivity: A chimeric study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31194/1/0000096.pd

Point Mutations in the 90-kDa Heat Shock Protein Binding Region of the Glucocorticoid Receptor Affect the Functional Characteristics of the Receptor a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72162/1/j.1749-6632.1995.tb31403.x.pd

Key Residues Defining the Μ-Opioid Receptor Binding Pocket: A Site-Directed Mutagenesis Study

Structural elements of the rat Μ-opioid receptor important in ligand receptor binding and selectivity were examined using a site-directed mutagenesis approach. Five single amino acid mutations were made, three that altered conserved residues in the Μ, Δ, and Κ receptors (Asn 150 to Ala, His 297 to Ala, and Tyr 326 to Phe) and two designed to test for Μ/Δ selectivity (Ile 198 to Val and Val 202 to Ile). Mutation of His 297 in transmembrane domain 6 (TM6) resulted in no detectable binding with [ 3 H]DAMGO ( 3 H-labeled d-Ala 2 , N -Me-Phe 4 ,Gly-ol 5 -enkephalin), [ 3 H]bremazocine, or [ 3 H]ethylketocyclazocine. Mutation of Asn 150 in TM3 produces a three- to 20-fold increase in affinity for the opioid agonists morphine, DAMGO, fentanyl, Β-endorphin 1–31 , JOM-13, deltorphin II, dynorphin 1–13 , and U50,488, with no change in the binding of antagonists such as naloxone, naltrexone, naltrindole, and nor-binaltorphamine. In contrast, the Tyr 326 mutation in TM7 resulted in a decreased affinity for a wide spectrum of Μ, Δ, and Κ agonists and antagonists. Altering Val 202 to Ile in TM4 produced no change on ligand affinity, but Ile 198 to Val resulted in a four- to fivefold decreased affinity for the Μ agonists morphine and DAMGO, with no change in the binding affinities of Κ and Δ ligands.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65474/1/j.1471-4159.1997.68010344.x.pd