{'fraction_non_alphanumeric': 0.039119804400977995, 'fraction_numerical': 0.02750611246943765, 'mean_word_length': 5.820833333333334, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Evidence for β2-Adrenoceptor-Mediated Facilitation of 3H-Noradrenaline Release from Isolated Guinea Pig Papillary Muscles

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.