Influence of lithium on the positive inotropic effect of phenylephrine and isoprenaline in guinea-pig heart

Mantelli, Laura; Capanni, Lucia; Corti, Vittorio; Bennardini, Federico; Matucci, Rosanna; Ledda, F.

doi:10.1016/0014-2999(88)90757-1

Cited by 11 publications

(6 citation statements)

References 33 publications

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“…temperature, stimulation rate) are rather similar in the two studies. The findings of Mantelli et al (1988) are also in contrast to the findings of Molderings & Schiimann (1987) in guinea pig left atria. The contrasting results may be due to species differences and differences between atrial and ventricular myocardium, but the action of lithium may also be complex and the resultant effect may be critically dependent upon yet unknown factors T. SKOMEDAL ET AL (see above).…”

Section: Discussioncontrasting

confidence: 89%

“…In order to test the possibility that the inositol phosphate moiety might be involved in mediating the a,-adrenergic inotropic effect in ventricular rat myocardium, the a,-adrenergic inotropic response was evaluated in the absence and the presence of lithium. In accordance with the findings in guinea pig left atria (Molderings & Schiimann 1987) and in contrast to the findings in guinea pig myocardium (Mantelli et al 1988) the present data showed that lithium increased the maximal a,-adrenoceptor mediated inotropic effect. The P-adrenoceptor mediated inotropic response was influenced rather in the opposite way by lithium.…”

supporting

confidence: 90%

“…(1987) and Scholz et al (1987 & 1988) reported an increase in inositol phosphates preceding the mechanical response to a,-adrenoceptor stimulation in rat atria in the presence of lithium (10 mmol/l). However, Mantelli et al (1988) reported that lithium had an inhibiting effect upon the a,-adrenoceptor mediated inotropic response in guinea pig ventricular myocardium.…”

mentioning

confidence: 97%

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Lithium Increases the α₁‐Adrenoceptor Mediated Inotropic Effect in Rat Heart

Skomedal

Schiander

Husøy

et al. 1991

Pharmacology & Toxicology

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The intracellular mechanisms activated by stimulation of myocardial alpha 1-adrenoceptors are not known. As in several other tissues, however, activation of alpha 1-adrenoceptors in heart has been related to breakdown of phosphoinositides resulting in production of putative intracellular messengers: different inositol phosphates and diacylglycerol. Lithium has been shown to inhibit enzymes hydrolyzing inositol phosphates. In the present paper we report studies on the effect of lithium upon the alpha 1-adrenoceptor mediated inotropic response elicited in electrically driven rat papillary muscles. While there was no shift of the horizontal positioning of the dose-response curve to alpha 1-adrenergic stimulation in the presence of lithium, the alpha 1-adrenoceptor mediated inotropic effect was increased in a concentration dependent manner (0.25 to 3.0 mmol/l lithium). For comparison, the effect of lithium upon the beta-adrenoceptor mediated inotropic response was also studied. At 3.0 mmol/l lithium, the horizontal position of the dose-response curve to beta-adrenoceptor stimulation was shifted significantly to the right (to higher agonist concentrations) and the maximal beta-adrenoceptor mediated inotropic response was slightly although not significantly reduced. Thus the augmenting effect of lithium upon the alpha 1-adrenoceptor mediated response was specific for this receptor type. Although the effect of lithium may be complex, the data are compatible with the hypothesis that the inositol phosphates may be of functional importance during stimulation of myocardial alpha 1-adrenoceptors.

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Section: Discussioncontrasting

confidence: 89%

supporting

confidence: 90%

mentioning

confidence: 97%

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Lithium Increases the α₁‐Adrenoceptor Mediated Inotropic Effect in Rat Heart

Skomedal

Schiander

Husøy

et al. 1991

Pharmacology & Toxicology

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“…It would be of considerable interest to know whether clear functional effects of Li' in brain (e.g. Worley et al, 1988) can be inhibited by myo-inositol, as there is growing evidence for such reversals in the action of Li' in various cell division and embryonic development models (Forer & Sillers, 1987;Busa & Gimlich, 1989), as well as in lymphocyte activation (Mustelin et al, 1986) and in ac-adrenoceptor effects on the heart (Mantelli et al, 1988). Collectively, this strongly implicates phosphoinositide metabolism in multiple cellular functions and highlights the potent and selective actions of Li+ on this signalling system.…”

Section: Discussionmentioning

confidence: 99%

Reduced inositol polyphosphate accumulation and inositol supply induced by lithium in stimulated cerebral cortex slices

Kennedy

Challiss

Ragan

et al. 1990

Biochemical Journal

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The ability of lithium to interfere with phosphoinositide metabolism in rat cerebral cortex slices has been examined by monitoring the accumulation of CMP-phosphatidate (CMP-PtdOH) and the reduction in Ins(1,4,5)P3 and Ins(1,3,4,5)P4 levels. A small accumulation of [14C]CMP-PtdOH was seen in slices prelabelled with [14C]cytidine and stimulated with carbachol (1 mM) or Li+ (1 mM). However, simultaneous addition of both agents for 30 min produced a 22-fold accumulation, with Li+ producing a half-maximal effect at a concentration of 0.61 +/- 0.19 mM. Kinetic studies revealed that the effects of carbachol and Li+ on CMP-PtdOH accumulation occurred with no initial lag apparent under these conditions and that preincubation with myo-inositol (10 or 30 mM) dramatically attenuated CMP-PtdOH accumulation. myo-Inositol could also attenuate the rate of accumulation of CMP-PtdOH when added 20 min after carbachol and Li+; these effects were not observed when equimolar concentrations of scyllo-inositol were added. Use of specific radioreceptor assays allowed the mass accumulations of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 to be monitored. Following a lag of 5-10 min, Li+ resulted in a marked reduction in the accumulation of both inositol polyphosphates resulting from muscarinic-cholinergic stimulation. Preincubation of cerebral cortex slices with myo- (but not scyllo-) inositol delayed, but did not prevent, the reduction in the accumulation of Ins(1,4,5)P3 or Ins(1,3,4,5)P4. The results suggest that cerebral cortex, at least in vitro, is very sensitive to myo-inositol depletion under conditions of muscarinic receptor stimulation. The relationship of such depletion to the generation of inositol polyphosphate second messengers is discussed.

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“…Inhibitory actions of Li' have also been observed in peripheral tissues; in lymphocytes Ptdlns turnover and ornithine decarboxylase induction are decreased by Li' treatment [26], and in guinea-pig heart the positive inotropic effects of phenylephrine, but not isoprenaline, are blocked by Li' [27]. These latter effects were reversed by myo-inositol [26,27], suggesting that maintenance of free inositol concentrations is essential for continued functioning of cellular responses linked to inositide turnover.…”

Section: Discussionmentioning

confidence: 99%

Potentiation by lithium of CMP-phosphatidate formation in carbachol-stimulated rat cerebral-cortical slices and its reversal by myo-inositol

Godfrey

1989

Biochemical Journal

117

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This paper describes a rapid and simple method for measuring CMP-phosphatidate (CMP-PA; CDP-diacylglycerol), providing a novel assay for inositol phospholipid metabolism. Rat cerebral-cortical slices labelled with [14C]cytidine were incubated with the muscarinic cholinergic agonist carbachol in the presence of various concentrations of LiCl; 10 mM-LiCl greatly enhanced the carbachol-stimulated formation of [14C]CMP-PA over a 60 min incubation period. The potentiation by Li+ was concentration-dependent, with a maximal enhancement at 3 mM and half-maximal enhancement at 0.6 mM-LiCl. The enhancement by Li+ could be reversed by incubation with myo-inositol; a maximal effect was observed with 10 mM-inositol. A similar, though smaller, enhancement of CMP-PA concentrations in the presence of LiCl was observed in slices stimulated with noradrenaline, 5-hydroxytryptamine and K+. The results are discussed in relation to previously observed effects of Li+ on inositol phospholipid metabolism.

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Influence of lithium on the positive inotropic effect of phenylephrine and isoprenaline in guinea-pig heart

Cited by 11 publications

References 33 publications

Lithium Increases the α₁‐Adrenoceptor Mediated Inotropic Effect in Rat Heart

Lithium Increases the α₁‐Adrenoceptor Mediated Inotropic Effect in Rat Heart

Reduced inositol polyphosphate accumulation and inositol supply induced by lithium in stimulated cerebral cortex slices

Potentiation by lithium of CMP-phosphatidate formation in carbachol-stimulated rat cerebral-cortical slices and its reversal by myo-inositol

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Influence of lithium on the positive inotropic effect of phenylephrine and isoprenaline in guinea-pig heart

Cited by 11 publications

References 33 publications

Lithium Increases the α1‐Adrenoceptor Mediated Inotropic Effect in Rat Heart

Lithium Increases the α1‐Adrenoceptor Mediated Inotropic Effect in Rat Heart

Reduced inositol polyphosphate accumulation and inositol supply induced by lithium in stimulated cerebral cortex slices

Potentiation by lithium of CMP-phosphatidate formation in carbachol-stimulated rat cerebral-cortical slices and its reversal by myo-inositol

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Lithium Increases the α₁‐Adrenoceptor Mediated Inotropic Effect in Rat Heart

Lithium Increases the α₁‐Adrenoceptor Mediated Inotropic Effect in Rat Heart