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. 1992 May;106(1):115–122. doi: 10.1111/j.1476-5381.1992.tb14302.x

The effect of pertussis toxin on beta-adrenoceptor responses in isolated cardiac myocytes from noradrenaline-treated guinea-pigs and patients with cardiac failure.

L A Brown 1, S E Harding 1
PMCID: PMC1907432  PMID: 1324064

Abstract

1. A decreased responsiveness to the positive inotropic effects of beta-adrenoceptor agonists is a characteristic of human heart failure. We have investigated the involvement of inhibitory guanine nucleotide binding proteins (G-proteins) in this process using pertussis toxin treatment of isolated cardiac myocytes. 2. Myocytes isolated from failing human myocardium had a reduced maximum contractile response to isoprenaline relative to that for maximally stimulating concentrations of calcium, giving an isoprenaline/calcium ratio of 0.71 +/- 0.06 (n = 7 patients). This was significantly lower than in myocytes from non-failing myocardium, where the isoprenaline/calcium ratio was 1.16 +/- 0.07 (n = 6, P less than 0.001). Responses to high calcium were unchanged. 3. Myocytes were treated with pertussis toxin for 3-5 h at 35 degrees C. Successful inactivation of inhibitory G-proteins by pertussis toxin treatment was indicated by a loss of responsiveness to 10 microM adenosine (in the presence of submaximal isoprenaline). 4. Following pertussis toxin treatment of the myocytes from failing human heart the isoprenaline/calcium ratio increased to 1.43 +/- 0.27 (n = 7, P less than 0.05). Pertussis toxin treatment had no effect upon the maximum calcium contraction. The isoprenaline/calcium ratio in myocytes from non-failing human ventricle was not affected by the toxin treatment (n = 3). These observations support the hypothesis that increased inhibitory G-protein levels or activities contribute to beta-adrenoceptor desensitization in human heart failure. 5. beta-Adrenoceptor desensitization in human heart failure is thought to be secondary to raised noradrenaline levels in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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