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Biomedical subjects

D Cue

Publications and source records attributed to D Cue.

21 records · Page 2Linked to original sources

Actions of the brain-penetrating H2-antagonist zolantidine on histamine dynamics and metabolism in rat brain.

The effects of zolantidine, the first brain-penetrating H2-receptor antagonist, on the brain levels of histamine (HA) and the HA metabolite tele-methylhistamine (t-MH), the activity of histamine methyltransferase (HMT) and the brain HA turnover rates were investigated in rats. Zolantidine dimaleate (0.1 to 100 mg/kg, s.c.) had no effect on whole brain levels of HA or t-MH and no effect on brain HMT activity, when measured 30 min after administration. Furthermore, brain t-MH levels in pargyline-treated animals were unaffected by zolantidine (0.1 to 25 mg/kg), indicating the absence of an effect on brain HA turnover. In vitro, zolantidine was a potent competitive inhibitor of both brain and kidney HMT, with Ki values of 2.3 and 2.7 microM respectively. These results show that, despite the ability of zolantidine to inhibit HMT in vitro, large doses of this drug did not alter brain HA methylation or turnover in vivo, and they imply that blockade of post-synaptic H2-receptors does not change brain HA dynamics.

Animals↗

Structure and sequence divergence of two archaebacterial genes.

The DNA sequences of a region that includes the hisA gene of two related methanogenic archaebacteria, Methanococcus voltae and Methanococcus vannielii, have been compared. Both organisms show a similar genome organization in this region, displaying three open reading frames (ORFs) separated by regions of very high A + T content. Two of the ORFs, including ORFHisA, show significant DNA sequence homology. As might be expected for organisms having a genome that is A + T-rich, there is a high preference for A and U as the third base in codons. Although the regions upstream of the structural genes contain prokaryotic-like promoter sequences, it is not known whether they are recognized as promoters in these archaebacterial cells. A ribosome binding site, G-G-T-G, is located 6 base pairs preceding the ATG translation initiation sequence of both hisA genes. The sequences upstream of the two hisA genes show only limited sequence homology. The M. voltae intergenic region contains four tandemly arranged repetitions of an 11-base-pair sequence, whereas the M. vannielii sequence contains both direct and inverted repetitive sequences. Based on the degree of hisA sequence homology, we conclude that M. voltae and M. vannielii are less closely related taxonomically than are members of the enteric group of eubacteria.

Archaea↗