The role of polyamines in beta-adrenergic stimulation of calcium influx and membrane transport in rat heart.
The beta-adrenergic agonist 1-isoproterenol induced an early (less than 1 min) stimulation of endocytosis, amino acid transport and hexose transport, monitored by the temperature-sensitive uptake of horseradish peroxidase, alpha-aminoisobutyrate and 2-deoxyglucose, respectively, in rat ventricle cubes. This stimulation was time- and concentration-dependent and was maximum at 10(-8) M isoproterenol. The beta-adrenergic antagonist propranolol blocked isoproterenol stimulation of membrane transport, thereby confirming beta-adrenoceptor mediation; 2.5 mM EGTA, 1 mM LaCl2 and 100 microM verapamil blocked the hormonal response without affecting basal transport. The calcium ionophore A23187 caused an acute stimulation of endocytosis, hexose and amino acid transport. Isoproterenol rapidly (less than 30 s) stimulated 45Ca2+ influx. These data suggest that stimulus-response (stimulus-"transport") coupling is mediated by a rise in cytosolic Ca2+ concentration. A rapid (less than 30 to 60 s) increase in ornithine decarboxylase (ODC) activity, followed by an early (less than 1 to 2 min), sustained increase in putrescine, spermidine and spermine concentrations was evoked by 10(-7) M isoproterenol. The ODC inhibitor alpha-difluoromethylornithine (DFMO, 5 mM) suppressed the isoproterenol-induced increase in ODC and polyamine levels and the stimulation of 45Ca influx, endocytosis, hexose transport, and amino acid transport. Putrescine (0.5 mM) negated DFMO inhibition and restored the increase in polyamines, 45Ca influx, endocytosis, and transport of hexose and amino acid. These data suggest that polyamine synthesis is involved in isoproterenol stimulation of Ca2+ influx and membrane transport functions in ventricular myocardium. These findings are consistent with a model for signal transduction and stimulus-response coupling in which polyamines function as intracellular messengers to generate cytosolic Ca2+ signals by stimulating Ca2+ influx.
Fan
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Neurology Service, VA Lakeside Medical Center, Chicago, IL 60611.
Koenig
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D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000493:pharmacokinetics*; D015220:Calcium Channels / Q000187:drug effects*; D003847:Deoxyglucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology; D005260:Female; D006735:Horseradish Peroxidase / Q000378:metabolism; D007545:Isoproterenol / Q000493:pharmacokinetics*; D009206:Myocardium / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D000621:Aminoisobutyric Acids; D015220:Calcium Channels; D011073:Polyamines; D011943:Receptors, Adrenergic, beta; D003847:Deoxyglucose; D006735:Horseradish Peroxidase; D009955:Ornithine Decarboxylase; D007545:Isoproterenol; D002118:Calcium; D000518:Eflornithine