Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of papaverine, an inhibitor of the phosphodiesterase responsible for breakdown of cAMP, on the transepithelial sodium transport across the isolated frog skin was investigated. Serosal addition of papaverine caused initially an increase in the short-circuit current (SCC), a doubling of the cellular cAMP content and a depolarization of the intracellular potential under SCC conditions (Vscc). The initial increase in the SCC was followed by a pronounced decrease both in the SCC and in the natriferic action of antidiuretic hormone (ADH), but papaverine had no inhibitory effect on the ability of ADH to increase the cellular cAMP content. As SCC declines, no hyperpolarization was observed. The I/V relationship across the apical membrane during the inhibitory phase, revealed that papaverine reduces the sodium permeability of the apical membrane (PNaa) as well as intracellular sodium concentration. These observations and the previously noted effect of papaverine on Vscc indicates that papaverine must have an effect on the cellular Cl or K permeability. The basolateral Na,K,2Cl cotransporter was blocked with bumetanide, which should bring the cellular chloride in equilibrium. Bumetanide had no effect on basal SCC and Vscc. When papaverine was added to skins preincubated with bumetanide, the effect of papaverine on SCC and Vscc was unchanged. Therefore, the depolarization of Vscc, observed during the papaverine-induced inhibition of the SCC, must be due to a reduction in the cellular K permeability. In conclusion, it is suggested that papaverine reduces the sodium permeability of the apical membrane and the potassium permeability of the basolateral membrane of the frog skin epithelium.
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PMID:Papaverine reduces the sodium permeability of the apical membrane and the potassium permeability of the basolateral membrane in isolated frog skin. 132 Dec 50

Previously, we demonstrated that genistein stimulated Cl(-) secretion in the mouse jejunum (Baker MJ and Hamilton KL, Am J Physiol Cell Physiol 287: C1636-C1645, 2004); however, the mode of action of genistein still remains unclear. Here, we examined the activation of Cl(-) secretion by the modulation of phosphodiesterases (PDEs) by genistein (75 microM) in the mouse jejunum with the Ussing short-circuit current (I(sc)) technique. Drugs tested included theophylline (10 mM), a nonspecific PDE inhibitor; 8-methoxymethyl-3-isobutyl-1-methylxanthine (8-MM-IBMX; 100 microM), erythro-9-(2-hydroxyl-3-nonyl)-adenine (EHNA; 40 microM), milrinone (100 microM), and rolipram (40 and 100 microM), which are specific inhibitors of PDE1-PDE4, respectively. Theophylline stimulated a bumetanide-sensitive I(sc), indicative of Cl(-) secretion, and abolished genistein's stimulatory action on I(sc). Neither 8-MM-IBMX nor EHNA altered the basal I(sc) nor did these PDE inhibitors affect the stimulatory action of genistein on the I(sc) of the mouse jejunum. Rolipram had no effect on basal I(sc), but it reduced the genistein-stimulated I(sc) compared with time-matched control tissues. Milrinone stimulated a concentration-dependent increase in I(sc). Bumetanide (10 microM) inhibited 60 +/- 4% of milrinone-induced I(sc). Pretreating tissues with milrinone prevented genistein from stimulating I(sc), and pretreatment with genistein reduced the effect of milrinone on I(sc). H89 (50 microM), a PKA inhibitor, reduced the milrinone-stimulated I(sc). Likewise, H89 reduced the genistein-stimulated I(sc). Here, we demonstrate, for the first time, that genistein activates Cl(-) secretion of the mouse jejunum via inhibition of a PDE3-dependent pathway.
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PMID:Genistein stimulates electrogenic Cl- secretion via phosphodiesterase modulation in the mouse jejunum. 1953 15