SURI and Kir6.1 subunits of K(ATP)-channels are co-localized in retinal glial (Müller) cells

ATP-sensitive potassium channels (K(ATP)), unlike other inwardly rectifying potassium (Kir) channels, require two structurally diverse subunits to form functional channels: one member of the Kir6 channel family (Kir6.1 or Kir6.2), and one sulfonylurea receptor (SUR) of the ATP-binding cassette superfamily (SURI, SUR2A or SUR2B).We have previously shown that two pore-forming subunits of K(ATP)-channels are differently distributed in frog retina. Kir6.1 is localized in Miller (glial) cells, whereas Kir6.2 is found in neurons. Using immunocytochemistry, the present study reveals that in adult frog retina, SURI is restricted to Müller (glial) cells whereas SUR2A and SUR2B are found in neurons. These data suggest that functional K(ATP) channels in Müller cells may be formed by Kir6.1/SURI, and in neurons by Kir6.2/SUR2A and/or Kir6.2/SUR2B.     

Isolation and characterization of orbivirus genotypic variants

Orbivirus variants containing either RNA deletions or concatemeric RNAs have been isolated. A variant of Ibaraki virus (a member of the epizootic hemorrhagic disease of deer serogroup) contained an RNA 9 segment which had terminal sequences identical to RNA 9 of wild type virus but was approximately 140 base pairs (bp) shorter. In vitro translation showed that whereas RNA 9 of wild type virus generated the minor structural protein VP6 (molecular weight 38 K), the variant RNA 9 coded for a 32 K protein. Analysis of hybrid molecules formed after melting and reannealing mixtures of [32P]-pCp-labeled wild type and variant RNA 9 molecules indicated that generation of variant RNA 9 may have involved the loss of approximately 150 bp at a location 148 bp from one end of the wild type RNA molecule. Analysis of minor proteins generated by premature termination during in vitro translation of wild type and variant RNA 9 suggested that the deletion occurred towards the 3' end of the positive strand of wild type RNA 9. RNA genome segments 10 and 9 of bluetongue virus type 21 and Bunyip Creek (a Palyam serogroup member) respectively, were observed to form concatemers. Molecular weight estimates and T1 RNase mapping suggested that the concatemers were dimers in a 5'-3' to 5'-3' orientation. In vitro translation of dimeric RNAs yielded products apparently identical to those generated by monomeric RNAs. The possible ramifications of these results with respect to orbivirus evolution are discussed.     

Sex dimorphic alterations in postnatal brain catecholarnines after gestational morphine

The concentration of brain catecholamines was measured in the hypothalamus, preoptic area (POA), frontal cortex, cerebellum, and striatum of rats exposed in utero to morphine (5–10 mg/kg/twice daily) during gestation days 11–18. Prenatal morphine induced regionally specific, sexually dimorphic alterations in male and female norepinephrine (NE), and dopamine (DA) content at different postnatal ages. Prenatal morphine significantly increased NE content in the hypothalamus of both sexes at postnatal day (PND) 23. In the POA, on the other hand, morphine increased NE content in exposed males at PND 23 and in females at PND 33. In the cerebellum, the NE content of both sexes was significantly elevated at PND 45. In the striatum, NE content was increased by the prenatal morphine only in females at PND 16. The concentration of DA was also affected in a sexually dimorphic manner. At PND 16, prenatal morphine increased the levels of hypothalamic DA only in males, and it reduced the content of DA in female but not male PDA. At PND 45, prenatal morphine increased DA in the hypothalamus of females and decreased it in males. In the cerebellum of 16-day-old morphine-exposed animals, DA levels were increased only in males; at PND 45, the levels of DA were still increased in males but had not changed in females. In the striatum, the DA content was reduced only in males at PND 16. Thus, prenatal morphine alters the development of both NE and DA neurotransmitter systems in the hypothalamus, POA, striatum, and cerebellum in a sexually dimorphic manner.     

Characterization of opioid receptor-mediated regulation of incertohypothalamic dopamine neurons: lack of evidence for a role of 5-hydroxytryptaminergic neurons in mediating the stimulatory effects of morphine.

The purpose of the present study was to characterize opioid receptor-mediated regulation of incertohypothalamic dopaminergic (DA) neurons in the rat brain by examining the acute effects of selective mu or kappa opioid receptor agonists and antagonists on concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in the medial zona incerta (MZI) and the dorsomedial hypothalamic nucleus (DMN) which contain cell bodies and terminals, respectively, of these neurons. Morphine caused a dose- and time-related increase in concentrations of DOPAC in MZI and DMN; this stimulatory effect was blocked by the mu opioid receptor antagonist naltrexone. In contrast, activation or blockade of kappa opioid receptors following administration of U-50,488 or nor-binaltorphimine, respectively, had no effect on DOPAC concentrations in either the MZI or DMN. The basal activity of incertohypothalamic DA neurons and their response to morphine was similar in male and female rats. Morphine also increased the concentrations of 5-hydroxyindoleacetic acid in MZI and DMN, indicating that morphine increases the activity of 5-hydroxytryptamine (5HT) neurons projecting to these regions. This might suggest that morphine-induced activation of incertohypothalamic DA neurons is mediated by 5HT neurons; but 5,7-dihydroxytryptamine-induced lesions of 5HT neurons did not alter the ability of morphine to increase DOPAC concentrations in MZI and DMN. These results indicate that the stimulatory effects of mu opioid receptor activation on incertohypothalamic DA neurons is not dependent upon the presence of 5HT neurons.     

Differential inhibition of nicotine- and acetylcholine-evoked currents through alpha4beta2 neuronal nicotinic receptors by tobacco cembranoids in Xenopus oocytes

In tobacco, there are two types of compounds that interact with neuronal nicotinic acetylcholine receptors (nnAChRs) in the brain. The first is the addictive component of tobacco and an agonist of these receptors, nicotine. The second are cyclic diterpenoids called cembranoids that non-competitively inhibit many types of nnAChRs. Nictotinic receptors composed of alpha4beta2 subunits are the predominant type of nicotinic receptors in the brain. These alpha4beta2 receptors are up-regulated upon chronic exposure to nicotine and have been implicated in nicotine addiction. The present study was designed to determine whether the inhibitory effects of two cembranoids from tobacco [(1S, 2E, 4R, 6R, 7E, 11E)-2,7,11-cembratriene-4,6-diol (4R) and its diastereoisomer (1S, 2E, 4S, 6R, 7E, 11E)-2,7,11-cembratriene-4,6-diol (4S)] were comparable on acetylcholine (ACh) and nicotine-evoked currents through alpha4beta2 nnAChRs. alpha4beta2 nnAChRs from rat brain were expressed in Xenopus oocytes and studied using the two-electrode voltage-clamp technique. The dose-response curves for acetylcholine and nicotine were hyperbolic and bell-shaped, respectively. Although there was no difference in the potency between cembranoids 4R and 4S, both of these cembranoids more potently inhibited nicotine-induced currents than acetylcholine-induced currents. Furthermore, both cembranoids were more potent inhibitors of this receptor when they were preincubated for 1 min prior to application of agonist. The finding that cembranoids preferentially inhibit nicotine-induced currents over those elicited by the natural neurotransmitter acetylcholine may have important implications when developing strategies to prevent nicotine addiction and tobacco use.     

The longitudinal relationship between personality disorder dimensions and global functioning in a community-residing population

BACKGROUND: Little is known about the long-term outcome of personality disorder traits. The purpose of this study was to investigate, in a community-residing population, the longitudinal relationship between psychiatrist-assessed personality disorder scores and global functioning 13-18 years later. METHOD: A stratified random sample of residents of east Baltimore were examined by psychiatrists in 1981 and asssessed for DSM-III personality disorders using a semi-structured instrument, the Standardized Psychiatric Examination. A total of 292 persons were re-examined by different psychiatrists during 1994-1999 using the Schedules for the Assessment of Neuropsychiatry (SCAN). After completion of the SCAN, the subjects' functional status was evaluated using the Global Assessment of Functioning (GAF). The relationships between personality dimensions and follow-up GAF scores were evaluated using linear regression models. RESULTS: All of the personality disorder scales measured in 1981 were inversely related to functioning 13-18 years later, with the exception of narcissistic and compulsive scales. After controlling for Axis I disorders diagnosed contemporaneously with GAF assessment, schizoid, antisocial, borderline, histrionic, and avoidant personality disorder scores significantly predicted GAF scores. CONCLUSIONS: Most dimensions of DSM-III personality disorder traits were significantly associated with global functioning after an interval of 15 years. However, only schizoid, antisocial, borderline, histrionic, and avoidant personality disorder traits had long-term effects on functioning when Axis I disorders at follow-up were controlled. This suggests that the functional effect of the other personality disorder traits may be mediated through their relationship with Axis I disorders. Future research is needed using more specific and sensitive outcome measures.