Mutations in Arg143 and Lys192 of the Human Mast Cell Chymase Markedly Affect the Activity of Five Potent Human Chymase Inhibitors.

Chymotrypsin-like serine proteases are found in high abundance in mast cell granules. By site-directed mutatgenesis, we have previously shown that basic amino acids in positions 143 and 192 (Arg and Lys respectively) of the human mast cell chymase are responsible for an acidic amino acid residue preference in the P2' position of substrates. In order to study the influence of these two residues in determining the specificity of chymase inhibitors, we have synthesized five different potent inhibitors of the human chymase.

Carbonic anhydrase inhibitors: the X-ray crystal structure of ethoxzolamide complexed to human isoform II reveals the importance of thr200 and gln92 for obtaining tight-binding inhibitors.

Ethoxzolamide, an almost forgotten inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.

Seromucosal transport of intravenously administered carbamazepine is not enhanced by oral doses of activated charcoal in rats.

The fate of carbamazepine after intravenous injection in rats (n = 24) and the influence of activated charcoal on the kinetics was investigated. After randomization to four groups (n = 6, each), plasma concentration and the quantities of carbamazepine and metabolites excreted into bile, urine and intestine were determined using an in situ perfusion model of the small intestine (Ringer's solution) with or without orally administered activated charcoal (AC+; AC-) and with or without bile duct cannulation (BD+; BD-). The cumulative amount of carbamazepine and metabolites exsorbed into the small intestine within 3.