Effects of xamoterol on inotropic and lusitropic properties of the human myocardium and on adenylate cyclase activity

Böhm, Michael; Mittmann, Clemens; Schwinger, Robert H. G.; Erdmann, Erland

doi:10.1016/0002-8703(90)90252-s

Cited by 13 publications

(4 citation statements)

References 40 publications

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“…(5) The protein concentration was determined by the method of Lowry. V 1A -R levels were measured by saturation of radioligand 125 I-p-AVP (PerkinElmer, NEX310010UC) binding.…”

Section: To the Editormentioning

confidence: 99%

Increased Vasopressin 1A Receptor Expression in Failing Human Hearts

Zhu

Tilley

Myers

et al. 2014

Journal of the American College of Cardiology

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“…(5) The protein concentration was determined by the method of Lowry. V 1A -R levels were measured by saturation of radioligand 125 I-p-AVP (PerkinElmer, NEX310010UC) binding.…”

Section: To the Editormentioning

confidence: 99%

Increased Vasopressin 1A Receptor Expression in Failing Human Hearts

Zhu

Tilley

Myers

et al. 2014

Journal of the American College of Cardiology

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“…However, beneficial effects could not be shown for all ␤-adrenoceptor antagonists. Xamoterol, a ␤ 1 -selective ␤-adrenoceptor antagonist with intrinsic sympathomimetic activity (ISA) Böhm et al, 1990), increased mortality in heart failure patients (Xamoterol in Severe Heart Failure Study Group, 1990). It was assumed that the ISA of xamoterol was responsible for this negative outcome.…”

mentioning

confidence: 99%

Bucindolol Exerts Agonistic Activity on the Propranolol-Insensitive State of β₁-Adrenoceptors in Human Myocardium

Bundkirchen

Brixius²,

Bölck³

et al. 2002

J Pharmacol Exp Ther

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In congestive heart failure patients, treatment with ␤-adrenoceptor antagonists improves symptoms and decreases mortality. However, intrinsic sympathomimetic activity of ␤-adrenoceptor antagonists might be disadvantageous in chronic heart failure. The nonselective ␤ 1 -and ␤ 2 -adrenoceptor antagonist bucindolol has failed to decrease mortality in clinical trials. A putative ␤ 4 -adrenoceptor, which mediates positive inotropic effects by activation of the adenylate cyclase has been described. Recently, this putative ␤ 4 -adrenoceptor has been identified to be a propranolol-insensitive state of the ␤ 1 -adrenoceptor. The present study aimed to characterize whether bucindolol exhibits agonistic activity on this atypical ␤ 1 -adrenoceptor state as one possible reason for clinical inefficiency.

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“…Membranes from human platelets (Jakobs et al 1982) and myometrium (Gsell et al 2000) were prepared as described. Membranes from human ventricles and liver were prepared at 4°C as described previously (Böhm et al 1990) with minor modifications. Frozen tissue (200-1000 mg) was minced to fine powder in liquid nitrogen with a mortar and homogenized in 5 ml buffer A [mM: TRIS 20, pH 7.4, EDTA 1, phenylmethylsulphonyl fluoride (PMSF) 1] with a Polytron (Kinematica, Littau, Switzerland, 4×15 s, setting 5) and subsequently with a Teflon/glass homogenizer (Colora, Lorch, Germany, 10×, setting 4).…”

Section: Methodsmentioning

confidence: 99%

Evidence for a short form of RGS3 preferentially expressed in the human heart

Mittmann

Schüler²,

Chung³

et al. 2001

Naunyn-Schmiedeberg's Archives of Pharmacology

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RGS proteins (regulators of G protein signalling) negatively regulate G protein function as GTPase-activating proteins (GAP) for G protein alpha-subunits. The existence of mRNAs of different size for some of the RGS proteins, e.g. RGS3, suggests that these proteins may exist in isoforms due to alternative splicing. We therefore investigated RGS3 mRNA and protein expression in different human tissues. Ribonuclease protection assays and Northern blot analysis showed two specific mRNAs for RGS3 (RGS3L, RGS3S) in human myocardium, suggesting an additional, N-terminally truncated form of approximately 168 aa. When expressed as a recombinant protein RGS3S was recognized at approximately 23 kDa by an antipeptide antiserum originally raised against an RGS2 sequence. In membranes of human tissues this antiserum detected specific signals for RGS3L (approximately 70 kDa), RGS2 (approximately 30 kDa) and a 25-kDa protein, most likely RGS3S. Both RGS3S mRNA and the 25 kDa protein were abundant in human heart, whereas expression in liver, brain and myometrium was much weaker. To characterize RGS3S functionally, single turnover GTPase, adenylyl cyclase (AC) and phospholipase C (PLC) activities were determined. Both recombinant RGS3S and RGS16 increased Pi release from Galphai1 by about 150% and increased GTP- and GTP plus isoprenaline-stimulated AC activity by 20-30% in human left ventricular myocardial membranes. Additionally, both RGS proteins reduced basal and endothelin-stimulated PLC activity in these membranes by about 40%. We conclude that an additional truncated form of RGS3 is expressed in the human heart. As described for the full-length protein, RGS3S negatively regulates the activity of Gi/o- and Gq-, but not Gs-subfamily members.

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Effects of xamoterol on inotropic and lusitropic properties of the human myocardium and on adenylate cyclase activity

Cited by 13 publications

References 40 publications

Increased Vasopressin 1A Receptor Expression in Failing Human Hearts

Increased Vasopressin 1A Receptor Expression in Failing Human Hearts

Bucindolol Exerts Agonistic Activity on the Propranolol-Insensitive State of β₁-Adrenoceptors in Human Myocardium

Evidence for a short form of RGS3 preferentially expressed in the human heart

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Effects of xamoterol on inotropic and lusitropic properties of the human myocardium and on adenylate cyclase activity

Cited by 13 publications

References 40 publications

Increased Vasopressin 1A Receptor Expression in Failing Human Hearts

Increased Vasopressin 1A Receptor Expression in Failing Human Hearts

Bucindolol Exerts Agonistic Activity on the Propranolol-Insensitive State of β1-Adrenoceptors in Human Myocardium

Evidence for a short form of RGS3 preferentially expressed in the human heart

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Bucindolol Exerts Agonistic Activity on the Propranolol-Insensitive State of β₁-Adrenoceptors in Human Myocardium