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 beta-adrenergic receptors (beta-ARs) coupled to pepsinogen secretion on frog esophageal peptic cells have been compared to frog erythrocyte beta-ARs using the radioligand 125I-iodopindolol (125I-PIN). 125I-PIN binding to intact peptic cells was time and temperature dependent. Saturation and competition experiments established that a large component of this binding represented radioligand uptake, which was energy dependent, pH sensitive, Na+ independent, and inhibited by agents that depress cellular ATP or disrupt proton gradients. This uptake system, which was absent from frog erythrocytes, appeared similar to that recently described for a number of mammalian cells. 125I-PIN bound to a single class of sites on peptic cell homogenates with a KD = 64 (+/- 5) pM. Binding to cell homogenates and a proportion of the binding to intact cells was inhibited by beta-agonists and antagonists with pharmacological characteristics similar to typical beta 2-ARs of frog erythrocytes. The number of beta-ARs in these peptic cell preparations was 1300 (+/- 240) sites/cell. Isolated peptic cells were poorly responsive to isoproterenol stimulation even in the presence of the phosphodiesterase inhibitor IBMX (3-isobutyl-1-methylxanthine). Pretreatment of cells with the phorbol ester TPA (12-O-tetra-decanoylphorbol-13-acetate) (100 nM) promoted isoproterenol stimulation of pepsinogen secretion. Catecholamine agonists stimulated pepsinogen secretion with an order of potency: isoproterenol greater than epinephrine much greater than norepinephrine, which was identical to that determined for inhibition of 125I-PIN binding. These findings indicate that frog peptic cells contain beta 2-ARs functionally coupled to pepsinogen secretion.
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PMID:125I-iodopindolol binding to frog esophageal peptic cells. Detection of amine uptake and beta-adrenergic receptors coupled to pepsinogen secretion. 254 27

Nuclear and cytoplasmic forms of the yeast exosome share 10 components, of which only Rrp44/Dis3 is believed to possess 3' exonuclease activity. We report that expression only of Rrp44 lacking 3'-exonuclease activity (Rrp44-exo) supports growth in S288c-related strains (BY4741). In BY4741, rrp44-exo was synthetic-lethal with loss of the cytoplasmic 5'-exonuclease Xrn1, indicating block of mRNA turnover, but not with loss of the nuclear 3'-exonuclease Rrp6. The RNA processing phenotype of rrp44-exo was milder than that seen on Rrp44 depletion, indicating that Rrp44-exo retains important functions. Recombinant Rrp44 was shown to possess manganese-dependent endonuclease activity in vitro that was abolished by four point mutations in the putative metal binding residues of its N-terminal PIN domain. Rrp44 lacking both exonuclease and endonuclease activity failed to support growth in strains depleted of endogenous Rrp44. Strains expressing Rrp44-exo and Rrp44-endo-exo exhibited different RNA processing patterns in vivo suggesting Rrp44-dependent endonucleolytic cleavages in the 5'-ETS and ITS2 regions of the pre-rRNA. Finally, the N-terminal PIN domain was shown to be necessary and sufficient for association with the core exosome, indicating its dual function as a nuclease and structural element.
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PMID:The N-terminal PIN domain of the exosome subunit Rrp44 harbors endonuclease activity and tethers Rrp44 to the yeast core exosome. 1912 31