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Effects of blockade of extraneuronal uptake on responses to isoprenaline in perfused rat heart
Author(s) -
Picken Gwynneth M.,
Jarrott B.
Publication year - 1975
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1975.tb03030.x
Subject(s) - isoprenaline , inotrope , endocrinology , medicine , normetanephrine , chemistry , metanephrine , antagonist , adrenergic receptor , epinephrine , catecholamine , receptor , biology , stimulation
SUMMARY1 Isolated rat hearts accumulated 102 pmol/g wet wt/min of isoprenaline when perfused for 5 min with 0.6 μM (±)‐ 3 H‐isoprenaline. 2 The 3‐methoxy derivative of isoprenaline (‘methoxy isoprenaline’) (10 μM) significantly inhibited this uptake by 57%, metanephrine (10 μM) by 29% and normetanephrine (10 μM) by 21%. 3 (±)‐Isoprenaline (0.6 μM) infused into isolated perfused rat hearts for 5 min activated glycogen phosphorylase 2.4‐fold. Normetanephrine (10 μM) or metanephrine (10 μM) included in the perfusate significantly potentiated this activation, but 3–0‐methyl isoprenaline (10 μM) significantly reduced it. However, 3–0‐methyl isoprenaline potentiated the ability of 4.8 μM isoprenaline to stimulate phosphorylase. 4 Neither metanephrine (10 μM) nor normetanephrine (10 μM) altered peak inotropic responses to injections of (±)‐isoprenaline into the solution perfusing isolated rat hearts. 3–0‐methyl isoprenaline (10 μM) shifted the isoprenaline dose‐response curve to the right, but did not affect the inotropic responses to CaCl 2 , confirming that 3–0‐methyl isoprenaline possesses β‐adrenoceptor antagonist activity. 5 Inotropic responses to isoprenaline were significantly prolonged by both 3–0‐methyl isoprenaline and normetanephrine (10 μM). 6 These results indicate that blockade of extraneuronal accumulation of catecholamines causes potentiation of both metabolic and mechanical β‐adreno‐ceptor‐mediated responses of the heart to isoprenaline. It is suggested that Uptake 2 and the cardiac β‐adrenoceptor are separate entities, and that the β‐adrenoceptor is localized in the sarcolemma. The physiological function of Uptake 2 may be to help clear the sympathetic synaptic gap of liberated neurotransmitter.