The ?-adrenergic receptors (?-ARs) are important modulators in the sympathetic control of various metabolic processes in the central (CNS) and peripheral nervous system. These receptors are localized at multiple sites throughout the nervous system, and serve as important regulators of CNS-mediated behavior and several neural functions, including mood, memory, neuroendocrine control, and stimulation of autonomic function. My laboratory has cloned, sequenced, and expressed the rat and rhesus macaque ?1-adrenergic receptor genes. We have defined the ?1-AR transcriptional start sites, promoter elements, and polyadenylation sites used for expression in the C6 glioma cell line, and have identified potential enhancer and repressor regions that influence ?1-AR expression. We have demonstrated that the inducible cAMP early repressor (ICER) is induced in C6 cells by ?1-AR agonists, and that ICER interacts with the ?1-AR promoter to down-regulate ?1-AR mRNA transcription, w ith resul tant diminution of cell surface receptor. We have also shown that the rat ?1-AR mRNA contains two functional polyadenylation sites, and that transcript selection occurs in C6 cells undergoing isoproterenol-induced ?1-AR mRNA down-regulation. This process may be regulated by post-transcriptional control mechanisms, potentially with the use of RNA stability proteins interacting with an AU-rich ?1-AR 3' untranslated region. Current research is centered on identifying genomic elements and trans-activators of ?1-AR transcription, with the use of ?1-AR luciferase-reporter recombinants, transfection assays, DNA mobility shift and DNase footprinting assays. The overall focus of this project is to precisely identify functional regulatory elements and factors involved in the regulation of the ?1-adrenergic receptor gene, and to analyze the transcriptional activation of the ?1-adrenergic receptor subtype during receptor down-regulation and hormonal stimulation. Research will initially utiliz e rodent tissues, prior to the use of nonhuman primate tissues, in the identification of ?1-AR transactivators. FUNDING NIH HL42358, and American Heart Association Established Investigator Award PUBLICATIONS Li Z, Vaidya RVA, Alvaro JD, Iredale PA, Hsu R, Hoffman G, Fitzgerald L, Curran PK, Machida CA, Fishman PH, Duman RS. Protein kinase C-mediated down-regulation of ?1-AR gene expression in rat C6 glioma cells. Mol Pharmacol 54:14-21, 1998. Yang YF, Kirigiti P, Li B, Deshmane S, Machida CA. Differential selection of ?1-adrenergic receptor transcripts during agonist-induced down-regulation. Soc Neurosci Abstr 24:600, 1998 (abstract 237.20).

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
7P51RR000163-41
Application #
6312854
Study Section
Project Start
1978-05-01
Project End
2004-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
41
Fiscal Year
2000
Total Cost
$116,898
Indirect Cost
Name
Oregon Health and Science University
Department
Type
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Okoye, Afam A; Hansen, Scott G; Vaidya, Mukta et al. (2018) Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound. Nat Med 24:1430-1440
Jensen, Jeffrey T; Hanna, Carol; Mishler, Emily et al. (2018) Effect of menstrual cycle phase and hormonal treatments on evaluation of tubal patency in baboons. J Med Primatol 47:40-45
Toro, C A; Aylwin, C F; Lomniczi, A (2018) Hypothalamic epigenetics driving female puberty. J Neuroendocrinol 30:e12589
Bulgarelli, Daiane L; Ting, Alison Y; Gordon, Brenda J et al. (2018) Development of macaque secondary follicles exposed to neutral red prior to 3-dimensional culture. J Assist Reprod Genet 35:71-79
Prola-Netto, Joao; Woods, Mark; Roberts, Victoria H J et al. (2018) Gadolinium Chelate Safety in Pregnancy: Barely Detectable Gadolinium Levels in the Juvenile Nonhuman Primate after in Utero Exposure. Radiology 286:122-128
Moccetti, Federico; Brown, Eran; Xie, Aris et al. (2018) Myocardial Infarction Produces Sustained Proinflammatory Endothelial Activation in Remote Arteries. J Am Coll Cardiol 72:1015-1026
Blue, Steven W; Winchell, Andrea J; Kaucher, Amy V et al. (2018) Simultaneous quantitation of multiple contraceptive hormones in human serum by LC-MS/MS. Contraception 97:363-369
Jeon, Sookyoung; Li, Qiyao; Rubakhin, Stanislav S et al. (2018) 13C-lutein is differentially distributed in tissues of an adult female rhesus macaque following a single oral administration: a pilot study. Nutr Res :
Slayden, Ov Daniel; Friason, Francis Kathryn E; Bond, Kise Rosen et al. (2018) Hormonal regulation of oviductal glycoprotein 1 (OVGP1; MUC9) in the rhesus macaque cervix. J Med Primatol 47:362-370
Dissen, G A; Adachi, K; Lomniczi, A et al. (2017) Engineering a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update. Reprod Domest Anim 52 Suppl 2:354-358

Showing the most recent 10 out of 492 publications