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Inotropic changes induced by fluoroaluminates in rabbit left atrial muscles: possible involvement of G proteins
Author(s) -
Hattori Yuichi,
Imamura Michialki,
Akaishi Yasuhiro,
Kanno Morio
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb14929.x
Subject(s) - inotrope , isoprenaline , medicine , endocrinology , contraction (grammar) , chemistry , histamine , pertussis toxin , muscle contraction , contractility , calcium , g protein , stimulation , receptor
1 The effects of fluoroaluminate complexes (NaF plus AlCl 3 ) on force of contraction, cyclic AMP accumulation and phosphoinositide hydrolysis were examined in rabbit left atrial muscles. 2 Fluoroaluminates (1–10 m m NaF + 10 μ m AlCl 3 ) produced a biphasic inotropic response which was composed of an early small decline and subsequent increase in force of contraction. In the presence of the Al 3+ chelator, deferoxamine (100 μ m ), the positive inotropic response was completely abolished and a sustained negative inotropic response appeared, suggesting that only the positive inotropic response is due to the action of fluoroaluminates. 3 The positive inotropic effect of fluoroaluminates was associated with a significant increase in the total duration of a single contraction; the time to peak tension and relaxation time were prolonged. In contrast, these parameters were substantially abbreviated by isoprenaline or histamine. 4 When force of contraction was increased by isoprenaline or histamine, the addition of fluoroaluminates caused a marked negative inotropic effect, which was eliminated by pretreatment with pertussis toxin. 5 Fluoroaluminates did not cause a significant increase in cyclic AMP content at concentrations of NaF in the range of 1–10 m m . However, the content of cyclic AMP was greatly elevated by fluoroaluminates when the atrial muscles were pretreated with pertussis toxin. 6 Accumulation of [ 3 H]‐inositol monophosphate in atrial muscle strips prelabelled with myo ‐[ 3 H]‐inositol was significantly increased by fluoroaluminates at concentrations of NaF over 1 m m . The phosphoinositide response to fluoroaluminates remained unchanged with pertussis toxin pretreatment. 7 These results indicate that, in rabbit left atrial muscles, fluoroaluminates produce a positive inotropic effect which may be mediated by G q but not by G s proteins; they produce a negative inotropic effect possibly through G i only when G s is activated with other agents.