title: Beta-adrenergic agonists stimulate the oxidative pentose phosphate pathway in the rat heart.
abstract: The oxidative pentose phosphate pathway is poorly developed in the rat heart compared with other organs, since the activity of glucose-6-phosphate dehydrogenase (G-6-PDH), the first and rate-limiting enzyme of the oxidative pentose phosphate pathway, is low. As a consequence, the available pool of 5-phosphoribosyl-1-pyrophosphate and the rate of adenine nucleotide biosynthesis are limited. Isoproterenol, 24 hours after subcutaneous administration at 0.1, 1, and 25 mg/kg, stimulated the activity of G-6-PDH in whole hearts dose-dependently from 4.3 +/- 0.16 (control) to 6.6 +/- 0.35, 10.3 +/- 0.82, and 11.5 +/- 0.56 units/g protein, respectively. The activity of 6-phosphogluconate dehydrogenase, another of the enzymes in the oxidative pentose phosphate pathway, remained unchanged. G-6-PDH activity started to increase 12 hours after isoproterenol application, when the glycogenolytic and functional response was over, and reached a peak value between 24 and 48 hours. This stimulating effect was also demonstrated in cardiac myocytes that were isolated 28 hours after isoproterenol application. beta-receptor blockade with atenolol reduced the isoproterenol-induced increase in cardiac G-6-PDH activity by 90%. Cycloheximide, which inhibits translation, and actinomycin D, which interferes with transcription, attenuated it by 83% and 78%, respectively. These results indicate that cardiac beta-adrenergic receptors and enzyme protein synthesis are involved in this effect. Other beta-sympathomimetic agents such as dopamine, dobutamine, fenoterol, salbutamol, and terbutaline also stimulated myocardial G-6-PDH activity in a time- and dose-related manner. The calcium antagonist D 600 (gallopamil) reduced the isoproterenol-elicited stimulation by 65%, and verapamil blunted the fenoterol-induced increase by 50%. This suggests that Ca2+ ions also contribute to the stimulation of the cardiac oxidative pentose phosphate pathway.
authors.affiliation: Department of Physiology, University of Munich, F.R.G.
authors.forename: H G
authors.initials: HG
authors.lastname: Zimmer
authors.forename: H
authors.initials: H
authors.lastname: Ibel
authors.forename: U
authors.initials: U
authors.lastname: Suchner
mesh_terms: D000227:Adenine Nucleotides / Q000096:biosynthesis; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005260:Female; D005280:Fenoterol / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012266:Ribose / Q000378:metabolism; D013268:Stimulation, Chemical; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000227:Adenine Nucleotides; D000318:Adrenergic beta-Agonists; D003609:Dactinomycin; D005280:Fenoterol; D005711:Gallopamil; D012266:Ribose; D003513:Cycloheximide; D014700:Verapamil; D005954:Glucosephosphate Dehydrogenase; D007545:Isoproterenol