Modulation of human cardiac function through 4 β-adrenoceptor populations
- Cite this article as:
- Kaumann, A. & Molenaar, P. Naunyn-Schmiedeberg's Arch Pharmacol (1997) 355: 667. doi:10.1007/PL00004999
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In human heart there is now evidence for the involvement of four β-adrenoceptor populations, three identical to the recombinant β1-, b2- and β3-adrenoceptors, and a fourth as yet uncloned putative β-adrenoceptor population, which we designate provisionally as the cardiac putative β4-adrenoceptor. This review described novel features of β-adrenoceptors as modulators of cardiac systolic and diastolic function. We also discuss evidence for modulation by unoccupied β1- and β2-adrenoceptors. Human cardiac and recombinant β1- and β2-adrenoceptors are both mainly coupled to adenylyl cyclase through Gs protein, the latter more tightly than the former. Activation of both human β1- and β2-adrenoceptors not only increases cardiac force during systole but also hastens relaxation through cyclic AMP-dependent phosphorylation of phospholamban and troponin I, thereby facilitating diastolic function. Furthermore, both β1 and β2-adrenoceptors can mediate experimental arrhythmias in human cardiac preparations elicited by noradrenaline and adrenaline. Human ventricular β3-adrenoceptors appear to be coupled to a pertussis toxin-sensitive protein (Gi?). β3-Adrenoceptor-selective agonists shorten the action potential and cause cardiodepression, suggesting direct coupling of a Gi protein to a K+ channel. In a variety of species, including man, cardiac putative β4-adrenoceptors mediate cardiostimulant effects of non-conventional partial agonists, i.e. high affinity β1- and β2-adrenoceptor blockers that cause agonist effects at concentrations considerably higher than those that block these receptors. Putative β4-adrenoceptors appear to be coupled positively to a cyclic AMP-dependent cascade and can undergo some desensitisation.