Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In order to distinguish between models of anion secretion, the effects of transport inhibitors on saliva flow rate and electrolyte composition were studied during the plateau phase of secretion in rabbit mandibular salivary glands. 2. Bumetanide, an inhibitor of Na+,K+,2Cl- co-transport, inhibited flow rate (by 60%) and reduced Cl- concentration. K+ and HCO3- concentrations were increased. Forskolin, an adenylate cyclase activator which inhibits ductal transport, did not significantly affect this pattern of changes. 3. Amiloride, used at concentrations that would inhibit Na(+)-H+ exchange, inhibited flow rate (by 30%). Cl- concentration was initially increased before subsequently decreasing at the same time as HCO3- concentration increased. These concentration changes can probably be attributed to ductal transport. When amiloride was applied to glands perfused with nominally HCO3- -free solutions, inhibition of flow rate was rapid and almost complete. 4. When amiloride and bumetanide were both present in the perfusate, flow rate was inhibited by 92%. The pattern of electrolyte changes was not significantly different from that observed in the presence of bumetanide alone. 5. Inhibition of K+ channel activity using Ba2+ also inhibited flow rate. Cl- concentration was increased as was K+ concentration. HCO3- concentration was not increased. 6. The anion exchange inhibitor DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) had no effect on either flow rate or electrolyte concentration. It did, however, elicit secretion in the absence of acetylcholine. 7. The data suggest that Na(+)-H+ and Cl- -HCO3- exchangers are unlikely to be involved in fluid and electrolyte secretion in these glands as suggested by some authors. Most of the data can be explained by postulating the existence of non-specific anion channels in the apical membranes of the acinar cells.
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PMID:The effects of bumetanide, amiloride and Ba2+ on fluid and electrolyte secretion in rabbit salivary gland. 221 84

Bak Foong Pills (BFP, also known as Bai Feng Wan) is an over-the-counter traditional Chinese medicine that has long been used for treating gynecological disorders and improving overall body functions, including gastrointestinal (GI) function. However, the cellular signaling mechanism underlying BFP action, especially on the GI tract, has not been elucidated. In the present study, the human colonic epithelia cell line T(84) was used as a model to investigate the effect of BFP ethanol extract on ion transport in conjunction with the short-circuit current (I(SC)) technique. The results showed that the apical addition of BFP extract produced a concentration-dependent (10-1,000 microg/ml, EC(50) = 120 microg/ml) increase in I(SC). The maximal response was observed at 500 microg/ml with an increase in I(SC) of 24.4 +/- 2.3 microA/cm(2) and apical conductance. The BFP-induced I(SC) was not observed when extracellular Cl(-) was replaced or when treated with Bumetanide (100 microM), an inhibitor of the Na(+)-K(+)-2Cl(-) cotransporter. The BFP-induced I(SC) was insensitive to the Na(+) channel blocker, amiloride, but partially inhibited by the Cl(-) channel blocker, DIDS (100 microM), and completely blocked by DPC (2 mM) or glibenclamide (1 mM) with a significant reduction in the apical conductance. The BFP-induced I(SC) could be mimicked by forskolin (10 microM), but inhibited by a pretreatment of the cells with adenylate cyclase inhibitor, MDL-12330A (10 microM). Pretreatment with EGTA (5 mM) and thapsigargin (10 microM) decreased the BFP-induced I(SC) by 10%. These results demonstrated that BFP ethanol extract exerted a stimulatory effect on gastrointestinal Cl(-) secretion by predominantly activating adenylate cyclase and apical cAMP-dependent Cl(-) channels, with minor contributions from calcium-dependent Cl(-) channels. The effect of BFP may be explored to treat GI disorders such as constipation.
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PMID:Cellular signaling mechanisms underlying pharmacological action of Bak Foong Pills on gastrointestinal secretion. 1204 11

We investigated the effects of 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one(DCEBIO) on the Cl- secretory response of the mouse jejunum using the Ussing short-circuit current (Isc) technique. DCEBIO stimulated a concentration-dependent, sustained increase in Isc (EC50 41 +/- 1 microM). Pretreating tissues with 0.25 microM forskolin reduced the concentration-dependent increase in Isc by DCEBIO and increased the EC50 (53 +/- 5 microM). Bumetanide blocked (82 +/- 5%) the DCEBIO-stimulated Isc consistent with Cl- secretion. DCEBIO was a more potent stimulator of Cl- secretion than its parent molecule, 1-ethyl-2-benzimidazolinone. Glibenclamide or NPPB reduced the DCEBIO-stimulated Isc by >80% indicating the participation of CFTR in the DCEBIO-stimulated Isc response. Clotrimazole reduced DCEBIO-stimulated Isc by 67 +/- 15%, suggesting the participation of the intermediate conductance Ca2+-activated K+ channel (IKCa) in the DCEBIO-activated Isc response. In the presence of maximum forskolin (10 microM), the DCEBIO response was reduced and biphasic, reaching a peak response of the change in Isc of 43 +/- 5 microA/cm2 and then falling to a steady-state response of 17 +/- 10 microA/cm2 compared with DCEBIO control tissues (61 +/- 6 microA/cm2). The forskolin-stimulated Isc in the presence of DCEBIO was reduced compared with forskolin control tissues. Similar results were observed with DCEBIO and 8-BrcAMP where adenylate cyclase was bypassed. H89, a PKA inhibitor, reduced the DCEBIO-activated Isc, providing evidence that DCEBIO increased Cl- secretion via a cAMP/PKA-dependent manner. These data suggest that DCEBIO stimulates Cl- secretion of the mouse jejunum and that DCEBIO targets components of the Cl- secretory mechanism.
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PMID:DCEBIO stimulates Cl- secretion in the mouse jejunum. 1613 45