Evidence for β2-Adrenoceptor-Mediated Facilitation of 3H-Noradrenaline Release from Isolated Guinea Pig Papillary Muscles

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Abstract
Summary: The effects of β-adrenoceptor agonists and antagonists on field-stimulated release of radioactivity from superfused guinea pig papillary muscles preincubated with 3H-noradrenaline were studied. Stimulation-evoked overflow of tritium was abolished in the absence of Ca2+ or the presence of tetrodotoxin. Isoprenaline (1 μmol/L) caused a slight facilitation of evoked overflow, whereas phentolamine (1 μmol/L) exerted a strong facilitatory action. However, when phentolamine (1 μmol/L) was present throughout superfusion, isoprenaline and the selective β2-adrenoceptor agonist, zinterol, caused concentration-dependent increases (half-maximal effects at 1 nmol/L). The effects of the agonists were inversely related to stimulation frequency. Furthermore, the concentration–response curve of isoprenaline was shifted to the right by the selective β2-adrenoceptor antagonist, ICI 118,551, but not by the selective β1-adrenoceptor antagonist, ICI 89,406. Schild-plot analysis revealed competitive antagonism and a pA2 value of 9.04 for ICI 118,551. Both ICI 118,551 and ICI 89,406, as well as β-adrenoceptor antagonists with intrinsic sympathomimetic activity (pindolol and celiprolol; 1 μmol/L), had no effect on stimulation-evoked overflow of tritium (phentolamine present). It is concluded that guinea pig papillary muscles are endowed with prejunctional β2 adrenoceptors facilitating impulse-evoked noradrenaline release. The facilitation is markedly promoted by blockade of prejunctional α adrenoceptors.

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