Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The substrate analogue 2-(1-carboxy-2-phenylethyl)-4-phenylazophenol is a potent competitive inhibitor of carboxypeptidase A. Upon ligation to the active site, the azophenol moiety undergoes a shift of pKa from a value of 8.76 to a value of 4.9; this provides an index of the Lewis acidity of the active site zinc ion. Examination of the pH dependence of Ki for the inhibitor shows maximum effectiveness in neutral solution (limiting Ki = 7.6 X 10(-7) M), with an increase in Ki in acid (pK1 = 6.16) and in alkaline solution (pK2 = 9.71, pK3 = 8.76). It is concluded that a proton-accepting enzymic functional group with the lower pKa (6.2) controls inhibitor binding, that ionization of this group is also manifested in the hydrolysis of peptide substrates (kcat/Km), and that the identity of this group is the water molecule that binds to the active site metal ion in the uncomplexed enzyme (H2OZn2+L3). Reverse protonation state inhibition is demonstrated, and conventional concepts regarding the mechanism of peptide hydrolysis by the enzyme are brought into question.
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PMID:A probe of the active site acidity of carboxypeptidase A. 371 30

Oral FPL-52694 [5-(2-hydroxypropoxy)-8-propyl-4-oxo-4H-1-benzopyran-2-carboxylic acid Na], a new mast cell stabilizer, dose-dependently inhibited gastric acid secretion but increased the volume and pepsin output in pylorus-ligated rats. Intraduodenal FPL-52694 significantly inhibited all of the volume, acidity, acid output and pepsin output. Concerning the acidity, oral administration of the agent showed much more potent inhibition than intraduodenal administration. Oral FPL-52694 markedly inhibited the development of pylorus-ligated ulcers, water-immersion stress- and aspirin-induced gastric erosions and moderately inhibited the formation of reserpine-induced gastric erosions in rats. Intraduodenal FPL-52694 also inhibited pylorus-ligated ulcers whereas it had no effect on aspirin-induced gastric erosions. Histamine-induced gastric erosions were not affected by oral FPL-52694. These effects of FPL-52694 were almost the same as those of cimetidine, except that cimetidine tended to inhibit histamine-induced gastric erosions. Although the precise mechanism of action of FPL-52694 remains unknown, oral FPL-52694 appears to be a promising agent for the treatment of peptic ulcers.
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PMID:Effects of FPL-52694, a new mast cell stabilizer, on gastric secretion and various acute gastric lesions in rats. 654 Sep 73

Morphine and tubocurarine may release histamine by direct mast cell degranulation which may result in systemic effects such as cutaneous flushing, local wheal and flare formation and hypotension. This randomised, double-blind study examined whether preoperative combined oral terfenadine (60 mg) and ranitidine (150 mg) attenuates the reduction in blood pressure and cutaneous flushing after the administration of tubocurarine and morphine in 60 patients undergoing elective gynaecological surgery. In addition, investigation was made of whether tubocurarine and morphine cause a significant decrease in gastric pH in comparison to the nonhistamine-releasing agents fentanyl and vecuronium. Patients were randomly assigned to one of three groups receiving either pre-operative terfenadine and ranitidine and intra-operative tubocurarine and morphine (group A); pre-operative placebo and intra-operative tubocurarine and morphine (group B); pre-operative placebo and intra-operative fentanyl and vecuronium (group C). Compared to group B, group A had less hypotension and tachycardia but no significant decrease in cutaneous flushing immediately following morphine and tubocurarine (p > 0.05). There were no significant differences in haemodynamic changes between the groups A and C. In those patients not pretreated with terfenadine and ranitidine (groups B and C), gastric pH decreased between 5 and 10 min following bolus administration of morphine and tubocurarine (group B), whereas patients receiving fentanyl and vecuronium (group C) had an increase in gastric pH. This suggests that histamine release following administration of morphine and tubocurarine is sufficient to increase gastric acidity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of the H1 and H2 receptor antagonists, terfenadine and ranitidine on the hypotensive and gastric pH effects of the histamine releasing drugs, morphine and tubocurarine. 821 91