Mechanism of noradrenaline-induced heterologous desensitization of adenylate cyclase stimulation in rat heart muscle cells: increase in the level of inhibitory G-protein α-subunits

Reithmann, Christopher; Gierschik, Peter; Sidiropoulos, Dimitrios N.; Werdan, Karl; Jakobs, Karl H.

doi:10.1016/0922-4106(89)90051-5

Cited by 114 publications

(37 citation statements)

References 30 publications

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“…Such a result is in accordance with that reported in the rat heart by Eschenhagen et al (1991Eschenhagen et al ( , 1992 who showed that the increase of G i 2 mRNA levels after in vivo isoprenaline infusion was due to an activation of gene transcription (Müller et al 1993). So, our present work and that of Eschenhagen's group extend some of the in vitro observations made previously on a canine kidney cell line (Rich et al 1984), in cultured rat heart muscle (Reithmann et al 1989) and S49 mouse lymphoma cells (Hadcock et al 1990). However, up-regulation of G i 2 levels in response to sustained activation of the stimulatory pathway is not a general feature since it has not been observed in NG 108-15 cells exposed to prostaglandin (PG) E 1 or forskolin (McKenzie & Milligan 1990) or in the human neuroblastoma cell line SK-N-MC treated with isoprenaline (Michel et al 1993).…”

Section: Discussionsupporting

confidence: 83%

In vivo stimulation of the beta(2)-adrenergic pathway increases expression of the Gi proteins and the alpha(2)A-adrenergic receptor genes in the pregnant rat myometrium

Lecrivain

Mhaouty-Kodja²,

Cohen‐Tannoudji³

et al. 1998

Journal of Endocrinology

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Cross-regulations between G s and G i mediated pathways controlling the adenylyl cyclase activity have been clearly demonstrated in vitro. To elucidate whether activation of the -adrenergic pathway in the pregnant myometrium might affect G i proteins and 2 -adrenergic receptors (ARs), we treated late pregnant rats from day 18 to day 21 with twice-daily administration of isoproterenol (8 mg/ kg). This treatment increased myometrial cAMP levels and led after 76 h to a significant and maximal rise in the immunoreactive amount of myometrial G i 2 and G i 3 proteins (1·4-and 1·7-fold respectively) associated with a parallel increase of the steady-state levels of both G i 2 and G i 3 mRNA (1·6-and 1·9-fold respectively). Propranolol antagonized this response indicating the implication of the -adrenergic pathway. Nuclear run-on assays demonstrated that isoproterenol enhanced respectively by 1·3-and 1·2-fold the transcription rate of the G i 2 and G i 3 genes. Quantification of myometrial 2 -ARs by [3 H]rauwolscine binding revealed that the total number of receptors was also increased at 76 h by 1·7-fold when compared with controls, with no change in the affinity of the 2 -ARs for the ligand. This effect was antagonized by propranolol. Quantification of both 2A -and 2B -subtypes by Northern blotting analysis demonstrated that this elevation was due to a selective increase of the 2A -subtype mRNAs. The present results indicate that in vivo stimulation of the -adrenergic pathway by isoproterenol increases both G i 2 /G i 3 and 2A -AR expression in the pregnant rat myometrium. The possible contribution of such a mechanism in pregnancy-related changes of both entities is discussed.

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Section: Discussionsupporting

confidence: 83%

In vivo stimulation of the beta(2)-adrenergic pathway increases expression of the Gi proteins and the alpha(2)A-adrenergic receptor genes in the pregnant rat myometrium

Lecrivain

Mhaouty-Kodja²,

Cohen‐Tannoudji³

et al. 1998

Journal of Endocrinology

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“…It is widely accepted that xs-GTP and/or fly directly interacts with the catalytic unit of adenylyl cyclase to stimulate cyclic AMP production. However, it is still unclear which of xci-GTP or fly subunits conveys the inhibition of adenylyl cyclase activity in vivo (Gilman, 1987;Reithmann, Gierschik, Sidiropoulos, Werdan & Jakobs, 1989;Wong, Federman, Pace, Zachary, Evans, Pouyssegur & Burp, 1991). Also it remains unclear to what extent G proteins sustain a spontaneous agonist-independent activation under in vivo conditions.…”

Section: Discussionmentioning

confidence: 99%

Agonist‐independent effects of muscarinic antagonists on Ca2+ and K+ currents in frog and rat cardiac cells.

Hanf

Szabó

et al. 1993

The Journal of Physiology

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SUMMARY1. The whole-cell patch clamp and intracellular perfusion techniques were used for studying the effects of atropine and other muscarinic acetylcholine receptor (mAChR) antagonists on the L-type calcium currents ('Ca) in frog and rat ventricular myocytes, and on the mAChR-activated K+ current ('K(ACh)) in frog atrial myocytes.2. In frog ventricular myocytes, atropine (01 nm to I /,tM) reversed the inhibitory effect of acetylcholine (ACh, 1 nM) on 'Ca previously stimulated by isoprenaline (Iso, 2 JM), a /l-adrenergic agonist. However, in the concomitant presence of Iso, ACh and atropine, 'Ca was > 50 % larger than in Iso alone.3. The effects of atropine were then examined in the absence of mAChR agonists. 4. Atropine (1 M) had no effect on frog ICa (i) under basal conditions, (ii) upon stimulation of ICa by the dihydropyridine agonist (-)-Bay K 8644 (1 aM), or (iii) when ICa had been previously stimulated by intracellular perfusion with cyclic AMP (3 AM). However, atropine increased Jca after a stimulation by forskolin (0 3 1M).Therefore, an increased adenylyl cyclase activity was required for atropine to produce its stimulatory effect on Jca 5. The order of potency of mAChR antagonists to reverse the inhibitory effect of ACh on Iso elevated ICa in frog ventricle was atropine > AF-DX 116 > pirenzepine.In the absence of ACh, mAChR antagonists produced their stimulatory effect on Iso elevated ICa with the same order of potency.6. Intracellular substitution of Gpp(NH)p (5'-guanylylimidiphosphate) for GTP (420 AtM) induced a strong inhibition of frog Ica in the presence of Iso (2 aM).

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“…(Feldman et al, 1988;Neumann et al, 1988). Secondly, long-term in vitro treatment of rat cardiomyocytes with noradrenaline causes a shift in the GdGi-ratio towards elevated Gi-protein (Reithmann et al, 1989). Thirdly, long-term in vitro treatment of a variety of cell types with agonists inhibiting adenylate cyclase (such as somatostatin, opiates, muscarinic cholinoceptor, a2-adrenoceptor or adenosine) desensitizes receptor coupling to inhibition of adenylate cyclase and simultaneously potentiates the stimulating effects of various hormones on adenylate cyclase (for references see Thomas & Hoffman, 1987 (Brodde et al, 1984;Gille et al, 1985; could be located on the same cells as fl-adrenoceptors.…”

Section: Resultsmentioning

confidence: 99%

Chronic β₁‐adrenoceptor antagonist treatment sensitizes β₂‐adrenoceptors, but desensitizes M₂‐muscarinic receptors in the human right atrium

Motomura¹,

Deighton²,

Zerkowski

et al. 1990

British J Pharmacology

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1 In 64 patients undergoing coronary artery bypass grafting the effects of chronic fl1-adrenoceptor antagonist (metoprolol, atenolol, bisoprolol) treatment on right atrial fi-adrenoceptor and muscarinic M2-receptor number and functional responsiveness were investigated.2 The fil-adrenoceptor antagonists increased right atrial fl,-adrenoceptor number, did not affect fl2-adrenoceptor number, and decreased muscarinic M2-receptor number. 3 Concomitantly, activation of right atrial adenylate cyclase by 1OuM GTP, 10pM isoprenaline and 1 UM forskolin was enhanced and inhibition by 100pM carbachol was diminished. 4 On isolated, electrically driven right atria the 6,1-adrenoceptor-mediated positive inotropic effect of noradrenaline was -even with fil-adrenoceptor number increased -not altered, while the fi2-adrenoceptor-mediated effect of procaterol was markedly enhanced. However, the carbachol-induced negative inotropic effect was decreased.5 It is concluded that chronic fl1-adrenoceptor antagonist treatment increases fil-adrenoceptor number and concomitantly sensitizes f2-adrenoceptor function, but desensitizes muscarinic M2-receptor function in the human heart.

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Mechanism of noradrenaline-induced heterologous desensitization of adenylate cyclase stimulation in rat heart muscle cells: increase in the level of inhibitory G-protein α-subunits

Cited by 114 publications

References 30 publications

In vivo stimulation of the beta(2)-adrenergic pathway increases expression of the Gi proteins and the alpha(2)A-adrenergic receptor genes in the pregnant rat myometrium

In vivo stimulation of the beta(2)-adrenergic pathway increases expression of the Gi proteins and the alpha(2)A-adrenergic receptor genes in the pregnant rat myometrium

Agonist‐independent effects of muscarinic antagonists on Ca2+ and K+ currents in frog and rat cardiac cells.

Chronic β₁‐adrenoceptor antagonist treatment sensitizes β₂‐adrenoceptors, but desensitizes M₂‐muscarinic receptors in the human right atrium

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Mechanism of noradrenaline-induced heterologous desensitization of adenylate cyclase stimulation in rat heart muscle cells: increase in the level of inhibitory G-protein α-subunits

Cited by 114 publications

References 30 publications

In vivo stimulation of the beta(2)-adrenergic pathway increases expression of the Gi proteins and the alpha(2)A-adrenergic receptor genes in the pregnant rat myometrium

In vivo stimulation of the beta(2)-adrenergic pathway increases expression of the Gi proteins and the alpha(2)A-adrenergic receptor genes in the pregnant rat myometrium

Agonist‐independent effects of muscarinic antagonists on Ca2+ and K+ currents in frog and rat cardiac cells.

Chronic β1‐adrenoceptor antagonist treatment sensitizes β2‐adrenoceptors, but desensitizes M2‐muscarinic receptors in the human right atrium

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Chronic β₁‐adrenoceptor antagonist treatment sensitizes β₂‐adrenoceptors, but desensitizes M₂‐muscarinic receptors in the human right atrium