Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that captopril (CP) inhibits ADH-stimulated osmotic water permeability (Pf) in the toad bladder by potentiating endogenous bradykinin (BK). The present studies examine the effect of CP on ADH-stimulated Pf in isolated, perfused rabbit cortical collecting tubules (CCT). CP (10(-4) M) reversibly inhibited Pf, stimulated by maximal concentrations of ADH (10 microU/ml). Pretreatment of CCT's with 5 microM indomethacin, however, abolished the effect of CP. Inhibition of BK production by the kallikrein inhibitors, aprotinin and benzamidine, failed to enhance Pf stimulated by submaximal concentrations of ADH (2.5 microU/ml). Since ADH exerts its effects by activation of adenylyl cyclase (AC), further experiments were performed to identify the site at which CP inhibits this cascade. CP significantly inhibited forskolin (10(-4) M) stimulated Pf; however, it had no effect on cyclic AMP (10(-5) M) stimulated Pf, suggesting that the site of action is on the catalytic subunit or one of the GTP regulatory proteins of AC. To further localize the site of CP's action, CCT's were pre-incubated with pertussis toxin (0.5 microgram/ml) to inactivate the inhibitory, guanosine triphosphate (GTP) regulatory protein, Gi. In these tubules, CP failed to inhibit the action of ADH. We conclude that CP stimulates prostaglandin production which in turn activates Gi and inhibits AC activity. We further suggest that CP stimulates PG's directly, not via BK.
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PMID:Captopril inhibits the hydroosmotic effect of ADH in the cortical collecting tubule. 332 2

The water osmotic permeability of frog urinary bladder was found to be increased from 0.08 +/- 0.01 to 1.28 +/- 0.20 microl/min cm2 when serosal bathing medium was changed 4 times for a fresh Ringer solution. High epithelium permeability is accompanied by an increased content of cyclic AMP in the bladder tissue (by 42%, P < 0.01), higher activity of both basal and forskolin-stimulated membrane adenylate cyclase (AC) (by 109% and 74%, respectively, P < 0.05) and by appearance of aggregates of intramembranous particles in the apical membrane. The water flow was inhibited by 10(-9)-10(-5) M prostaglandin E2 (PGE2); the inhibitory effect was eliminated in the presence of 10(-4) M N-ethylmaleimide. The increase of water permeability due to changes of the bathing medium was accompanied by a decrease of serosal PGE2 concentration from 14.8 +/- 1.0 in the 1st solution to 0.6 +/- 0.1 nM in the 5th. 10(-6) M PGE2 in vitro inhibited the activity of membrane AC from highly permeable bladders by 33.4% (P < 0.02). Pretreatment of the membranes with 10 microg/ml pertussis toxin (PT) completely reversed this effect (+149%, P < 0.01). A significant activation of AC was also observed under 10(-10) M PGE2 (by 196%). These data demonstrate that the water permeability could be markedly increased independently of ADH, suggesting that the trigger role in activation of water transport is played by a decreased level of PGE2 which could stimulate AC.
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PMID:Role of prostaglandin E2 in regulation of low and high water osmotic permeability in frog urinary bladder. 915 Feb 74