86Rubidium efflux and negative inotropy induced by P1- and muscarinic-receptor agonists in guinea-pig left atria

Urquhart, Robert A.; Rothaul, Alan L.; Broadley, Kenneth J.

doi:10.1016/0006-2952(91)90329-4

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…Urquhart et al [34] showed that 4-AP (10 mM) virtually abolished rubidium efflux stimulated by R-PIA in guinea-pig left atria whereas here the onset of the functional response was only slowed. 4-AP also prevented R-PIA from stopping the right atria beating.…”

Section: Negutiw Clironotropic Rc~sponses To R-piamentioning

confidence: 63%

“…The apparent non-competitive antagonism of R-PIA is not contrary to a competitive inhibition of K+-channels by 4-AP since the interaction is not at the A,-receptor level but down-stream at the ion channel level which is equivalent to a functional antagonism. Urquhart et al [34] showed that 4-AP (10 mM) virtually abolished rubidium efflux stimulated by R-PIA in guinea-pig left atria whereas here the onset of the functional response was only slowed. It is reasonable to suggest, therefore, that only a component of the response to R-PIA in guinea-pig right atria is blocked by 10 mM 4-AP which is mediated by K+-efflux through adenosine A ,-receptor operated channels.…”

Section: Negutiw Clironotropic Rc~sponses To R-piamentioning

confidence: 63%

“…Stimulation of adenosine A, -receptors by R-(-)-Nh-(2-phenylisopropyl)-adenosine (R-PIA) in left atria causes an efflux of K+ [ I ] . The efflux of radiolabelled Rb+ induced by R-PIA as a marker of K+-efflux is almost completely blocked by 10 mM 4-aminopyridine (4-AP) [34]. The role of K+ in the development of the negative inotropic response of left atria to R-PIA, however, is still the source of some controversy.…”

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confidence: 99%

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Effects of K+‐channel blockers on A₁‐adenosine receptor‐mediated negative inotropy and chronotropy of guinea‐pig isolated left and right atria

Ford

Broadley

1999

Fundamemntal Clinical Pharma

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Adenosine has previously been shown to stimulate K(+)-efflux and to block L-type calcium channels in atrial myocytes. The aim of the present study was to evaluate the contribution of K(+)-channels in the development of the negative inotropic and chronotropic responses to adenosine agonists in guinea-pig left and right atria, respectively. Tetraethylammonium (TEA) potentiated the negative inotropic and chronotropic responses to R-(-)-N6-(2-phenyl-isopropyl)-adenosine (R-PIA), seen as leftward shifts of the concentration-response curves. Glibenclamide had no effect on the negative inotropic response to R-PIA but increased the rate of onset of the negative chronotropic response in right atria. 4-Aminopyridine (4-AP, 10 mM), potentiated the left atrial inotropic responses to R-PIA, seen as a leftward shift of the concentration-response curve, but slowed the speed of onset of the response to a single concentration (10(-6) M) of R-PIA. This reduction in speed of onset of the response can explain the differences in effects of 4-AP on concentration-response curves reported here and previously. In the right atria, 4-AP (10 mM) inhibited the negative chronotropic responses to R-PIA, seen as a rightward shift of the concentration-response curve and reduction of the maximum response. 4-AP also slowed the onset of the right atrial rate response to R-PIA. These results support the theory that K(+)-efflux plays only a minor role in the negative inotropic responses of guinea-pig left atria to R-PIA. This apparently controls the speed of onset of the response. The negative chronotropic response of guinea-pig right atria to R-PIA appears to be much more dependent upon K(+)-efflux than for the negative inotropic response of the left atria.

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Section: Negutiw Clironotropic Rc~sponses To R-piamentioning

confidence: 63%

Section: Negutiw Clironotropic Rc~sponses To R-piamentioning

confidence: 63%

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confidence: 99%

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Effects of K+‐channel blockers on A₁‐adenosine receptor‐mediated negative inotropy and chronotropy of guinea‐pig isolated left and right atria

Ford

Broadley

1999

Fundamemntal Clinical Pharma

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“…This receptor was xanthine sensitive, not coupled to adenylyl cyclase and produced effects by modulating calcium entry into cells ( Ribeiro & Sebastiao, 1986 ). Both K + efflux ( Belardinelli & Isenberg, 1983 ; Cerbai et al ., 1988 ; Visentin et al ., 1990 ; Urquhart et al ., 1991 ; 1993 ) and closure of L‐type calcium channels ( DeBiasi et al ., 1989 ; Fassina et al ., 1991 ; Jahnel et al ., 1992 ) have been implicated in the negative inotropic effects of adenosine analogues in the guinea‐pig left atria.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the atypical characteristics of adenosine receptors mediating negative inotropic and chronotropic responses of guinea‐pig isolated atria and papillary muscles

Gardner

Broadley

1999

British J Pharmacology

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1 Adenosine receptor(s) mediating negative inotropy of paced left atria, isoprenaline-stimulated paced left atria and papillary muscles, and negative chronotropy of spontaneously beating right atria were characterized. 2 Isometric tension of guinea-pig isolated paced left atria and left ventricular papillary muscles and rate of contraction of spontaneously beating right atria were recorded. Papillary muscles were prestimulated with isoprenaline (1610 78 M). Concentration-response curves (CRCs) for tension or rate reduction by N 6 -cyclopentyladenosine (CPA), the stereoisomers of N 6 -(2-phenylisopropyl)adenosine ((+)-PIA and (7) -(3-iodobenzyl)adenosine-5'-N-methyuromide (IB-MECA) revealed a potency order of CPA=(7)-PIA4NECA in right atria and papillary muscles, which is consistent with involvement of A 1 -receptors. The potency order in left atria was CPA=NECA4(7)-PIA4(+)-PIA4APNEA, which is not typical of A 1 adenosine receptors. Weak activity of APNEA and IB-MECA discounts involvement of A 3 receptors. 3 pA 2 values for the antagonism of CPA by 8(p-sulfophenyl)theophylline (8-SPT) were calculated from Schild plots (log concentration-ratio against log 8-SPT concentration), the unity slopes of which indicated competitive antagonism. The pA 2 value in the papillary muscles was signi®cantly higher than for atrial preparations, indicating a possible dierence in receptor characteristics between atrial and papillary muscle responses. 4 In left and right atria there was a limit to the displacement of the CPA CRCs at higher concentrations of 8-SPT. The 8-SPT-resistant component of the response is suggested to arise from duality of coupling of a common A 1 receptor through either dierent G proteins or G protein subunits to independent transduction pathways. The results with papillary muscles can be explained by a typical A 1 receptor coupled to a single transduction pathway.

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Effect of carbachol in the absence and presence of phenylephrine on Rb+ efflux and tension in rabbit left atria

Ray

MacLeod

1994

European Journal of Pharmacology

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86Rubidium efflux and negative inotropy induced by P1- and muscarinic-receptor agonists in guinea-pig left atria

Cited by 6 publications

References 25 publications

Effects of K+‐channel blockers on A₁‐adenosine receptor‐mediated negative inotropy and chronotropy of guinea‐pig isolated left and right atria

Effects of K+‐channel blockers on A₁‐adenosine receptor‐mediated negative inotropy and chronotropy of guinea‐pig isolated left and right atria

Analysis of the atypical characteristics of adenosine receptors mediating negative inotropic and chronotropic responses of guinea‐pig isolated atria and papillary muscles

Effect of carbachol in the absence and presence of phenylephrine on Rb+ efflux and tension in rabbit left atria

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86Rubidium efflux and negative inotropy induced by P1- and muscarinic-receptor agonists in guinea-pig left atria

Cited by 6 publications

References 25 publications

Effects of K+‐channel blockers on A1‐adenosine receptor‐mediated negative inotropy and chronotropy of guinea‐pig isolated left and right atria

Effects of K+‐channel blockers on A1‐adenosine receptor‐mediated negative inotropy and chronotropy of guinea‐pig isolated left and right atria

Analysis of the atypical characteristics of adenosine receptors mediating negative inotropic and chronotropic responses of guinea‐pig isolated atria and papillary muscles

Effect of carbachol in the absence and presence of phenylephrine on Rb+ efflux and tension in rabbit left atria

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Effects of K+‐channel blockers on A₁‐adenosine receptor‐mediated negative inotropy and chronotropy of guinea‐pig isolated left and right atria

Effects of K+‐channel blockers on A₁‐adenosine receptor‐mediated negative inotropy and chronotropy of guinea‐pig isolated left and right atria