8-Bromo-guanosine-3′,5′-monophosphate mimics the effect of acetylcholine on slow response action potential and contractile force in mammalian atrial myocardium

Kohlhardt, M.; Haap, K.

doi:10.1016/0022-2828(78)90015-9

Cited by 54 publications

(16 citation statements)

References 19 publications

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“…It is in line with a functional NO-cyclic GMP signaling pathway in the heart that cyclic GMP or derivatives can depress Fc (Nawrath 1976;1977;Kohlhardt & Haap, 1978) and the calcium current (Hartzell & Fischmeister, 1986;Levi et al, 1989;Wahler et al, 1990;Mery et al, 1991). Wahler and Dollinger (1995) showed that SIN-i inhibits mammalian cardiac calcium current through activation of a cyclic GMP-dependent protein kinase.…”

Section: Discussionmentioning

confidence: 75%

The ineffectiveness of the NO‐cyclic GMP signaling pathway in the atrial myocardium

Nawrath

Bäumner

Rupp

et al. 1995

British J Pharmacology

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1 This study was performed to determine whether nitric oxide (NO) has direct effects on force of contraction (Fc) in atrial myocardium from rats, rabbits, guinea-pigs, frogs, and man. 2 Glyceryl trinitrate, isosorbide dinitrate, 3-morpholino-sydnonimine hydrochloride (SIN-1), and Snitroso-N-acetylpenicillamine (SNAP) did not signficantly reduce Fc in the various preparations investigated, either given alone or after stimulation of a-or fi-adrenoceptors.3 SNAP did not change the time course of contractions in rat, guinea-pig and human preparations. 4 8-Bromo-guanosine-3':5'-cyclic monophosphate (8-Br-cyclic GMP) produced a negative inotropic effect in rat, guinea-pig and human atrial preparations and shortened time to peak tension and relaxation time in human preparations. 5 High K+ (85 mmol 1I`)-induced contracture in rat heart muscle was reduced by 8-Br-cyclic GMP but not by SIN-1. 6 N-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, failed to influence muscarinic effects on Fc or frequency from rat and guinea-pig hearts. 7 We conclude that NO, under the experimental conditions described here, has no direct effects on the heart, although cyclic GMP may be involved in the regulation of myocardial contraction.

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Section: Discussionmentioning

confidence: 75%

The ineffectiveness of the NO‐cyclic GMP signaling pathway in the atrial myocardium

Nawrath

Bäumner

Rupp

et al. 1995

British J Pharmacology

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“…Nawrath (1977) has reported that acetylcholine and cyclic GMP analogues appear to reduce 45Ca uptake in rabbit atria. In addition, Kohlhardt & Haap (1978) have shown that both 8-bromo-cylic GMP and acetylcholine inhibit the calcium-dependent ' slow response' action potentials in guinea-pig atria; and Ikemoto & Goto (1978) have reported that iontophoretic injections of cyclic GMP depress the overshoot and plateau of the action potential in frog atrium. These experiments, however, should be repeated under carefully controlled conditions, since various adenine and guanine 60 ACh ON 42K EFFLUX IN HEART nucleotides have been shown to produce marked changes in transmembrane currents in cardiac muscle (Tsuda, Yatani & Goto, 1978;Hartzell, 1979).…”

Section: Sodium Nitroprusside Experimentsmentioning

confidence: 99%

Are acetylcholine‐induced increases in 42K efflux mediated by intracellular cyclic GMP in turtle cardiac pace‐maker tissue?

Fleming¹,

Giles²,

Lederer³

1981

The Journal of Physiology

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SUMMARY1. 42K efflux has been measured from small strips of turtle sinus venosus tissue in order: (a) to characterize further the pharmacology of the acetylcholine response and (b) to test whether cyclic guanosine 3': 5'-monophosphoric acid (cyclic GMP) is the intracellular mediator of this response.2. The 42K wash-out curves show that the fractional escape rate (FER) of 42K efflux is nearly constant after 60-80 min, indicating that after this time period 42K FER is controlled by barrier-limited diffusion from a single intracellular compartment.3. The threshold of the dose-response relationship for the acetylcholine-induced increase in 42K FER is about 10-8 M and the Km is 2'75 x 10-7 in non-eserinized preparations.4. This acetylcholine response is completely blocked by atropine; but nicotinic blockers produce no detectable reduction of it. 5. Exogenous application of lipid-soluble analogues of cyclic GMP (dibutyryl or 8-bromo-cyclic GMP applied at 2-3 mm for 30 min) failed to mimic the acetylcholineinduced augmentation of 42K FER. 6. Experiments in which sodium nitroprusside (5 x 10-4 M for 30 min) was applied in order to stimulate the guanylate cyclase and hence produce a large, maintained increase in intracellular cyclic GMP failed to show a significant increase in 42K FER.7. When acetylcholine (10-6 M) was applied in the presence of O[Ca2+]o (in an attempt to inhibit the guanylate cyclase) there was no significant reduction in the acetylcholine-induced increases in 42K FER.8. Hence, these three indirect tests indicate that the muscarinic acetylcholineinduced increase in 42K FER in cardiac pace-maker tissue is unlikely to be mediated entirely by changes in the levels of intracellular cyclic GMP.

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“…The first hormonal effect on cyclic GMP levels to be discovered was that produced by ACh in rat ventricle (George, Polson, O'Toole & Goldberg, 1970) and since then many investigators have demonstrated increases in cyclic GMP levels in response to cholinergic agents in a variety of cardiac preparations (Kuo, Lee, Reyes, Walton, Donnelly & Greengard, 1972; George, Ignarro, Paddock, White & Kadowitz, 1975;Watanabe & Besch, 1975;Gardner & Allen, 1976;Ghanbari & McCarl, 1976;Brown, Polson, Krzanowski & Wiggins, 1980;Lincoln & Keely, 1981; Dobson, 1981;Endoh, Maruyama & lijima, 1985). Furthermore, extracellular application of cyclic GMP or membrane-permeable derivatives of cyclic GMP often decrease contractile force (Wilkerson, Paddock & George, 1976;Trautwein & Trube, 1976;Nawarth, 1977;Kohlhardt & Haap, 1978;Linden & Brooker, 1979;Endoh & Yamashita, 1981;. It has been proposed that the negative inotropic effect of cyclic GMP, like that of ACh, is mediated by a decrease in ICa because cyclic GMP decreases 45Ca flux (Nawrath, 1977), shortens action potential duration (Trautwein, Taniguchi & Noma, 1982), and inhibits Ca2+-dependent action potentials (Kohlhardt & Haap, 1978;Bkaily & Sperelakis, 1985;Wahler & Sperelakis, 1985).…”

Section: Introductionmentioning

confidence: 99%

Cyclic guanosine 3',5'‐monophosphate regulates the calcium current in single cells from frog ventricle.

Fischmeister

Hartzell

1987

The Journal of Physiology

188

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SUMMARY1. The effect of intracellular perfusion with cyclic AMP and cyclic GMP on Ca2+ current (ICa) was studied in single cells isolated from frog ventricle using the whole-cell patch-clamp technique and a perfused pipette.2. Intracellular perfusion with cyclic GMP (0-1-20 JtM) had no effect on the basal half-maximal effect of cyclic GMP was observed at 0-6,UM. Cyclic GMP had no significant effect on the shape of the ICa current-voltage relationship.3. The effect of cyclic GMP was specific to the 3', 5' form; 2', 3'-cyclic GMP had no effect.4. The effect of cyclic GMP was apparently not mediated by stimulation of cyclic-GMP-dependent protein kinase because 8-bromo-cyclic GMP, a very potent activator of the protein kinase, was without effect. 5. Cyclic GMP had no effect on Ica elevated by the non-hydrolysable 8-bromocyclic AMP. The effect of cyclic GMP on cyclic-AMP-elevated Ica was partially blocked by the phosphodiesterase inhibitor, methylisobutylxanthine. Thus, it was hypothesized that the effect of cyclic GMP was mediated by hydrolysis of cyclic AMP as a result of a stimulation of a cyclic nucleotide phosphodiesterase by cyclic GMP.6. The dose-response curve for cyclic AMP on Ica was well fitted by the Michaelis equation with a K50 (i.e. concentration of cyclic AMP at which response is 50 % of the maximum) of0-7 /LM and a maximal 11-fold stimulation of Ica* Cyclic GMP shifted the curve one log unit to the right and decreased the maximal stimulation to 8-6-fold.Thus, the effect of cyclic GMP appeared uncompetitive.7. The products of cyclic AMP and cyclic GMP hydrolysis, 5'-AMP and 5'-GMP, had no effect on ICa Furthermore, strong buffering of intracellular pH did not reduce the effect of cyclic GMP. 8. It is proposed that cyclic-GMP-stimulation of a cyclic nucleotide phosphodiesterase may be one of several mechanisms by which acetylcholine regulates ICa-* To whom correspondence should be addressed at

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8-Bromo-guanosine-3′,5′-monophosphate mimics the effect of acetylcholine on slow response action potential and contractile force in mammalian atrial myocardium

Cited by 54 publications

References 19 publications

The ineffectiveness of the NO‐cyclic GMP signaling pathway in the atrial myocardium

The ineffectiveness of the NO‐cyclic GMP signaling pathway in the atrial myocardium

Are acetylcholine‐induced increases in 42K efflux mediated by intracellular cyclic GMP in turtle cardiac pace‐maker tissue?

Cyclic guanosine 3',5'‐monophosphate regulates the calcium current in single cells from frog ventricle.

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