Inotropic changes induced by fluoroaluminates in rabbit left atrial muscles: possible involvement of G proteins.
1. The effects of fluoroaluminate complexes (NaF plus AlCl3) on force of contraction, cyclic AMP accumulation and phosphoinositide hydrolysis were examined in rabbit left atrial muscles. 2. Fluoroaluminates (1-10 mM NaF + 10 microM AlCl3) 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 Al3+ chelator, deferoxamine (100 microM), 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 mM. However, the content of cyclic AMP was greatly elevated by fluoroaluminates when the atrial muscles were pretreated with pertussis toxin. 6. Accumulation of [3H]-inositol monophosphate in atrial muscle strips prelabelled with myo-[3H]-inositol was significantly increased by fluoroaluminates at concentrations of NaF over 1 mM. 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 Gq but not by Gs proteins; they produce a negative inotropic effect possibly through Gi only when Gs is activated with other agents.
Hattori
Y
Y
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Imamura
M
M
Akaishi
Y
Y
Kanno
M
M
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D016279:Atrial Function, Left / Q000187:drug effects*; D000242:Cyclic AMP / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005461:Fluorine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D011817:Rabbits
C053629:fluoroaluminum; D005461:Fluorine; D000535:Aluminum; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D003676:Deferoxamine