Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The peripheral mechanisms by which ephedrine and caffeine influence thermogenesis were investigated in innervated rat interscapular brown adipose tissue (IBAT) by assessing its rate of oxygen consumption (MO2) in vitro. Dose-response measurements with tissues from intact or sympathectomized (6-OHDA) animals indicate that the thermogenic effects of low concentrations of ephedrine and also of caffeine are entirely dependent upon the presence of intact sympathetic nerve endings, and thus depend on presynaptic mechanisms. Direct postsynaptic stimulation of thermogenesis is only apparent at much higher concentrations, namely greater than 1 microM for ephedrine and greater than 2mM for caffeine. At subminimal concentrations that neither ephedrine nor caffeine influenced basal tissue respiration, they induced a 4-5-fold increase in basal MO2 when administered in combination, a synergistic response prevented by pre-treatment of the rat with 6-OHDA. Synergistic increases in IBAT respiration were also obtained when subminimal concentration of ephedrine was added to 3-propylxanthine (a specific inhibitor of phosphodiesterase), to 8-phenyltheophylline (a potent adenosine receptor antagonist) or to adenosine deaminase (for enzymatic inactivation of endogenous adenosine). Conversely, the marked synergism in thermogenic response with ephedrine + caffeine was reduced in the presence of 2-chloroadenosine (an adenosine analogue). In tissues from fasted rats, the ephedrine + caffeine synergism in thermogenic response, although attenuated, was nevertheless present. These studies therefore demonstrate that ephedrine, at doses comparable with therapeutic use, stimulates thermogenesis in BAT via sympathetically released NA. In addition, a synergistic interaction between caffeine and ephedrine on BAT thermogenesis is explained by ephedrine's enhancement of sympathetic neuronal release of NA, together with caffeine's dual ability to antagonize adenosine and to inhibit cellular phosphodiesterase activity.
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PMID:Peripheral mechanisms of thermogenesis induced by ephedrine and caffeine in brown adipose tissue. 188 57

The otd/Otx gene family encodes paired-like homeodomain proteins that are involved in the regulation of anterior head structure and sensory organ development. Using the yeast one-hybrid screen with a bait containing the Ret 4 site from the bovine rhodopsin promoter, we have cloned a new member of the family, Crx (Cone rod homeobox). Crx encodes a 299 amino acid residue protein with a paired-like homeodomain near its N terminus. In the adult, it is expressed predominantly in photoreceptors and pinealocytes. In the developing mouse retina, it is expressed by embryonic day 12.5 (E12.5). Recombinant Crx binds in vitro not only to the Ret 4 site but also to the Ret 1 and BAT-1 sites. In transient transfection studies, Crx transactivates rhodopsin promoter-reporter constructs. Its activity is synergistic with that of Nrl. Crx also binds to and transactivates the genes for several other photoreceptor cell-specific proteins (interphotoreceptor retinoid-binding protein, beta-phosphodiesterase, and arrestin). Human Crx maps to chromosome 19q13.3, the site of a cone rod dystrophy (CORDII). These studies implicate Crx as a potentially important regulator of photoreceptor cell development and gene expression and also identify it as a candidate gene for CORDII and other retinal diseases.
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PMID:Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes. 939 May 16