Adrenaline and noradrenaline stimulate adenylate cyclase predominantly through beta 2-adrenoceptors, producing up to 10 times more cyclic AMP per receptor than beta 1-adrenoceptor stimulation.
What are the relative roles of beta 1- and beta 2-adrenoceptors in mediating the effects of adrenaline and noradrenaline on contractile force and adenylate cyclase in human myocardium?
The study demonstrates that in human myocardium, beta 2-adrenoceptors play a predominant role in adenylate cyclase stimulation, while beta 1-adrenoceptors primarily mediate maximal contractile force, with beta 2-mediated contractility becoming more prominent in patients treated with beta 1-selective antagonists.
The stimulant effects of adrenaline and noradrenaline on contractile force and adenylate cyclase, mediated through beta 1 and beta 2-adrenoceptors, are analysed in isolated atrial and ventricular myocardium of man. The tissues were obtained from patients without advanced heart failure undergoing heart surgery. Usually, both adrenaline and noradrenaline stimulated adenylate cyclase predominantly through ventricular and atrial beta 2-adrenoceptors. Because the relative density of beta 2-adrenoceptors is usually smaller than that of beta 1-adrenoceptors, stimulation of one beta 2-adrenoceptor leads to the production of up to 10 times more cyclic AMP molecules than does stimulation of one beta 1-adrenoceptor. Adrenaline and noradrenaline maximally enhance contractile force through both atrial and ventricular beta 1-adrenoceptors. Adrenaline can also maximally enhance contractile force through atrial beta 2-adrenoceptors. In the ventricle, adrenaline increases force via beta 2-adrenoceptors by up to 60% of its maximal beta 1 response. Noradrenaline can increase atrial and ventricular contractile force through beta 2-adrenoceptors but only at high concentrations. Unexpectedly, in atria from patients treated with the beta 1-selective antagonist atenolol, contractile responses to adrenaline are markedly and selectively augmented through activation of beta 2-adrenoceptors. In atria from atenolol-treated patients equi-inotropic concentrations of adrenaline and noradrenaline acting through beta 2 and beta 1-adrenoceptors, respectively, cause similar increases of cyclic AMP and of cyclic AMP-dependent protein kinase activity.
Kaumann et al. (Fri,) conducted a other in Patients without advanced heart failure undergoing heart surgery. Adrenaline and noradrenaline was evaluated on Stimulation of adenylate cyclase and contractile force. Adrenaline and noradrenaline stimulate adenylate cyclase predominantly through beta 2-adrenoceptors, producing up to 10 times more cyclic AMP per receptor than beta 1-adrenoceptor stimulation.
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