Inhibition of Adenylate Cyclase of Catfish and Rat Hepatocyte Membranes BY 9-(Tetrahydro-2-Furyl)Adenine (SQ 22536)

Fabbri, Elena; Brighenti, L; Ottolenghi, C

doi:10.3109/14756369109069062

Cited by 45 publications

(28 citation statements)

References 25 publications

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“…In spite of this evidence, the present results indicate that such mechanisms probably do not contribute to the relaxation caused by either methyl or ethyl gallate in the guinea pig trachea. These observations are supported by the results showing that the selective adenylyl cyclase inhibitor SQ 22536 (Bertelé et al 1984;Fabbri et al 1991) and methylene blue and ODQ, which are soluble guanylyl cyclase inhibitors (Gruetter et al 1981;Ellis 1997;Hussain et al 1997), all failed to antagonise the relaxant responses. Taken together, such results are consistent with the concept that the relaxant responses caused by methyl and ethyl gallate in the guinea pig trachea are related to their ability to directly activate K + channels, mainly BKCa-sensitive to tetraethylamonium and charybdotoxin.…”

Section: Discussionsupporting

confidence: 72%

The mechanisms underlying the relaxant effect of methyl and ethyl gallates in the guinea pig trachea in vitro: contribution of potassium channels

Paulino

Pizollatti

Yunes

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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The relaxant response and the possible contribution of K+ channels to the relaxation caused by both methyl and ethyl gallates, two compounds isolated from the Brazilian medicinal plant Phyllanthus urinaria, were investigated in the guinea pig trachea in vitro. Both methyl and ethyl gallate (0.01-30 microM) caused graded and complete relaxation of the guinea pig trachea without epithelium, pre-contracted by histamine, with mean EC50 values of 1.8 (1.2-2.2) microM and 0.7 (0.6-0.8) microM, respectively, and Emax of both 100+/-0%. Response to ethyl, but not methyl gallate, was significantly shifted to the right, with no change in the maximum effect when the epithelium was removed. The increase in K+ concentration in the medium to 80 mM completely abolished the relaxant response caused by both methyl and ethyl gallate. In addition, tetraethylammonium (10 mM) reduced by 50+/-6% and 43+/-4% the relaxation caused by methyl and ethyl gallates. In contrast, glibenclamide (3 microM) shifted (by about two- and fourfold) the concentration-response curves for both methyl and ethyl gallates, with no changes in the maximum effect. Charybdotoxin (100 nM), but not apamin (100 nM), significantly blocked by 54+/-5% and 59+/-4% the relaxation of both methyl and ethyl gallates. In contrast, SQ 22536 (10 microM; a selective adenylyl cyclase inhibitor), methylene blue (10 microM) or ODQ (1 microM; a guanylyl cyclase inhibitor) did not significantly affect the relaxant response caused by either of the compounds. These results provide evidence that the relaxation caused by both methyl and ethyl gallates in the guinea pig trachea in vitro may involve the activation of large-conductance Ca2+-activated K+ channels, and, to a lesser extent, ATP-sensitive K+ channels. Such results extend our previous observations and are consistent with the notion that methyl and ethyl gallates are mainly responsible for the relaxant action previously demonstrated in the extract of this plant.

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Section: Discussionsupporting

confidence: 72%

The mechanisms underlying the relaxant effect of methyl and ethyl gallates in the guinea pig trachea in vitro: contribution of potassium channels

Paulino

Pizollatti

Yunes

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Thus, BK-mediated relaxation in the guinea pig bronchus, which was largely insensitive to ODQ, seems to involve a direct activation of Ca 2+ -activated K + channels, highly sensitive to IbTx and TEA and to a lesser extent to ChTx. In contrast, the cAMP pathway has apparently no major role in BK-induced relaxation in the guinea pig bronchus, as the selective protein kinase A antagonist SQ 22536 (Fabbri et al 1991) did not interfere with BK-mediated relaxation.…”

Section: Discussionmentioning

confidence: 74%

Contribution of nitric oxide, prostanoids and Ca 2+ -activated K + channels to the relaxant response of bradykinin in the guinea pig bronchus in vitro

Mazzuco

André

Calixto

2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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In the guinea pig bronchus with epithelium, pre-contracted with histamine, bradykinin (BK), lysyl-BK, prostaglandin E2 (PGE2), cromakalim and S-nitroso-N-acetylpenicillamine each caused graded relaxation with mean EC50s of 34 nM, 11 nM, 0.1 nM, 0.3 microM and 3.4 microM, respectively. The addition of NO synthase inhibitors N(W)-nitro-L-arginine (L-NOARG), N(G)-monomethyl-L-arginine or 7-nitroindazole reduced BK-induced relaxation by 41+/-6%, 59+/-4% and 51+/-2%, respectively. The inhibition of BK response caused by L-NOARG was completely reversed by L-, but not by D-arginine. Methylene blue and 6-(phenylamino)-5,8-quinolinedione (LY 83583) inhibited the BK response by 88+/-5% and 64+/-4%, while 1H-[1,2,4]oxadiazolo[4,3-a]quinolaxin- -one (ODQ) had no effect. However, ODQ almost abolished SNAP-induced relaxation. Indomethacin and the cyclo-oxygenase 2 (COX-2) inhibitor 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanon e (DFU) caused graded inhibtion of BK responses with mean IC50s of 60 nM and 0.6 nM, respectively. Addition of tetraethylammonium (TEA), charybdotoxin (ChTx), or iberotoxin (IbTx) inhibited BK-induced relaxation by 76+/-4%, 30+/-4% and 99+/-1%, respectively, but the relaxations of PGE2 and cromakalim were unaffected. In contrast, 4-aminopyridine, apamin or glibenclamide did not affect BK-induced relaxation. These results indicate that BK-induced epithelium-dependent relaxation in the guinea pig bronchus is partially mediated by release of NO or by NO-related substances, involving an activation of both cyclo-oxygenase 1 (COX-1) and COX-2 enzymes, through a cyclic guanosine monophosphate (cGMP)-independent mechanism. Furthermore, BK-induced relaxation involves an activation of high-conductance Ca(2+)-activated K+ channels highly sensitive to IbTx, and to a lesser extent to ChTx and TEA.

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“…Similar results were obtained with cholera toxin and dibutyryl cAMP (data not shown). Because some of the effects of forskolin have previously been ascribed to mechanisms that do not involve adenylate cyclase activation [25], experiments were performed using either L-858051 (an active water-soluble forskolin analogue [26], SQ-22536 (an inhibitor of adenylate cyclase [27], H-89 [28] and HA-1004 [29], inhibitors of PKA, or 1,9,dideoxy-forskolin (an inactive hydrophobic forskolin analogue [26]). Addition of either 100 µM forskolin or 100 µM L-858051 significantly inhibited 5-HT-induced accumulation of IPs (Fig.…”

Section: -Ht-induced Accumulation Of Ipsmentioning

confidence: 99%

Regulation of 5-hydroxytryptamine-induced calcium mobilization by cAMP-elevating agents in cultured canine tracheal smooth muscle cells

et al. 1996

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The effects of increases in cellular adenosine 3'5'-cyclic monophosphate (cAMP) on 5-hydroxytryptamine-(5-HT-) induced generation of inositol phosphates (IPs) and increases in intracellular Ca2+ ([Ca2+]i) were investigated using canine cultured tracheal smooth muscle cells (TSMCs). Cholera toxin and forskolin induced concentration- and time-dependent cAMP formation with half-maximal effects (-logEC50) produced at concentrations of 7.0 +/- 0.5 and 4.9 +/- 0.4 respectively. Pretreatment of TSMCs with either forskolin or dibutyryl cAMP inhibited 5-HT-stimulated responses. Even after treatment for 24h, these agents still inhibited the 5-HT-induced Ca2+ mobilization. The inhibitory effects of these agents produced both depression of the maximal response and a shift to the right of the concentration response curves of 5-HT. The water-soluble forskolin analogue L-858051 [7-deacetyl-7beta-(gamma-N-methylpiperazino)-butyryl forskolin] significantly inhibited the 5-HT-stimulated accumulation of IPs. In contrast, the addition of 1,9-dideoxy forskolin, an inactive forskolin analogue, had little effect on this response. Moreover, SQ-22536 [9-(tetrahydro-2-furanyl)-9-H-purin-6-amine], an inhibitor of adenylate cyclase, and both H-89 [N-(2-aminoethyl)-5-isoquinolinesulphonamide] and HA-1004[N-(2-guanidinoethyl)-5-isoquinolinesulphonamide], inhibitors of cAMP-dependent protein kinase (PKA), attenuated the ability of forskolin to inhibit the 5-HT-stimulated accumulation of IPs. These results suggest that activation of cAMP/PKA was involved in these inhibitory effects of forskolin. The AlF4--induced accumulation of IPs was inhibited by forskolin, suggesting that G protein(s) are directly activated by AlF4-- and uncoupled from phospholipase C by forskolin treatment. These results suggest that activation of cAMP/PKA might inhibit the 5-HT-stimulated phosphoinositide breakdown and consequently reduce the [Ca2+]i increase or inhibit both responses independently.

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Inhibition of Adenylate Cyclase of Catfish and Rat Hepatocyte Membranes BY 9-(Tetrahydro-2-Furyl)Adenine (SQ 22536)

Cited by 45 publications

References 25 publications

The mechanisms underlying the relaxant effect of methyl and ethyl gallates in the guinea pig trachea in vitro: contribution of potassium channels

The mechanisms underlying the relaxant effect of methyl and ethyl gallates in the guinea pig trachea in vitro: contribution of potassium channels

Contribution of nitric oxide, prostanoids and Ca 2+ -activated K + channels to the relaxant response of bradykinin in the guinea pig bronchus in vitro

Regulation of 5-hydroxytryptamine-induced calcium mobilization by cAMP-elevating agents in cultured canine tracheal smooth muscle cells

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