More severe cellular phenotype in human idiopathic dilated cardiomyopathy compared to ischemic heart disease.

Activation of the β-adrenergic receptor (βAR) pathway is the main mechanism of the heart to increase cardiac output via protein kinase A (PKA)-mediated phosphorylation of cellular target proteins, and perturbations therein may contribute to cardiac dysfunction in heart failure. In the present study a comprehensive analysis was made of mediators of the βAR pathway, myofilament properties and cardiac structure in patients with idiopathic (IDCM; n = 13) and ischemic (ISHD; n = 10) cardiomyopathy in comparison to non-failing hearts (donor; n = 10) for the following parameters: βAR density, G-coupled receptor kinases 2 and 5, stimulatory and inhibitory G-proteins, phosphorylation of myofilament targets of PKA, protein phosphatase 1, phospholamban, SERCA2a and single myocyte contractility. All parameters exhibited the expected alterations of heart failure, but for most of them the extent of alteration was greater in IDCM than in ISHD.

Do gene polymorphisms alone or in combination affect the function of human beta3-adrenoceptors?

Background And Purpose: beta(3)-Adrenoceptors mediate many important physiological functions, for example, in the urinary bladder. The corresponding gene is polymorphic, and the W64R (Trp64Arg) single nucleotide polymorphism has been associated with disease states such as obesity, type 2 diabetes and bladder dysfunction. While these clinical data suggest that the 64R variant is hypofunctional, previous in vitro studies in which this variant was generated by site-directed mutagenesis and subsequent transfection have not consistently confirmed this.

The effect of bladder outlet obstruction on alpha1- and beta-adrenoceptor expression and function.

Aims: To explore possible changes in expression and/or function of alpha(1)- and beta-adrenoceptor subtypes as a cause for bladder dysfunction in a rat model of bladder outlet obstruction (BOO).

Methods: BOO was induced in rats by partial urethral ligature. Contraction and relaxation experiments were performed with isolated bladder strips from BOO, sham-operated and non-operated (control) rats 7 days after BOO induction.

Tools to study beta3-adrenoceptors.

Beta(3)-adrenoceptors mediate some of the effects of catecholamines on tissues such as blood vessels or the urinary bladder and are putative targets for the treatment of diseases such as the overactive bladder syndrome. Progress in the understanding of the presence, function, and regulation of beta(3)-adrenoceptors has been hampered by a lack of highly specific tools. "Classical" beta(3)-adrenoceptor agonists such as BRL 37,344 [(R*, R*)-(+/-)-4[2-[(3-chlorophenyl)-2-hydroxyethyl) amino] propyl] phenoxyacetic acid] and CGP 12,177 [(+/-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one] are only partial agonists in many settings, have limited selectivity over other beta-adrenoceptor subtypes, and may additionally act on receptors other than beta-adrenoceptors.

Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate.

1 We have systematically reviewed the presence, functional responses and regulation of alpha(1)-, alpha(2)- and beta-adrenoceptors in the bladder, urethra and prostate, with special emphasis on human tissues and receptor subtypes. 2 Alpha(1)-adrenoceptors are only poorly expressed and play a limited functional role in the detrusor. Alpha(1)-adrenoceptors, particularly their alpha(1A)-subtype, show a more pronounced expression and promote contraction of the bladder neck, urethra and prostate to enhance bladder outlet resistance, particularly in elderly men with enlarged prostates.