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Biomedical subjects

M L Entman

Publications and source records attributed to M L Entman.

At least 181 records · Page 10Linked to original sources
PubMed1977

The effect of adenylate cyclase inhibitor (ACI) on guanylate cyclase, phosphodiesterase and other enzymes in heart.

The effect of an inhibitor of adenylate cyclase (ACI) was measured on some enzymes associated with cyclic nucleotide-regulated metabolism. Soluble guanylate cyclase was inhibited; both soluble and particulate cyclic GMP-phosphodiesterases were stimulated. Cyclic AMP phosphodiesterases were unaffected. In contrast, the activities of Na, K-ATPase, protein kinase, phosphorylase kinase, glycogen synthetase and a number of glycosidases were not altered by equipotent amounts of the inhibitor. It is concluded that this substance acts as a modulator of both cyclic AMP and cyclic GMP metabolism in heart and other tissues.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

The rate of calcium uptake into sarcoplasmic reticulum of cardiac muscle and skeletal muscle. Effects of cyclic AMP-dependent protein kinase and phosphorylase b kinase.

Calcium transport into sarcoplasmic reticulum fragments isolated from dog cardiac and mixed skeletal muscle (quadriceps) and from mixed fast (tibialis), pure fast (caudofemoralis) and pure slow (soleus) skeletal muscles from the cat was studied. Cyclic AMP-dependent protein kinase and phosphorylase b kinase stimulated the rate of calcium transport although some variability was observed. A specific protein kinase inhibitor prevented the effect of protein kinase but not of phosphorylase b kinase. The addition of cyclic AMP to the sarcoplasmic reticulum preparations in the absence of protein kinase had only a slight stimulatory effect despite the presence of endogenous protein kinase. Cyclic AMP-dependent protein kinase catalyzed the phosphorylation of several components present in the sarcoplasmic reticulum fragments; a 19000 to 21 000 dalton peak was phosphorylated with high specific activity in sarcoplasmic reticulum preparations isolated from heart and from slow skeletal muscle, but not from fast skeletal muscle. Phosphorylase b kinase phosphorylated a peak of molecular weight 95000 in all of the preparations. Cyclic AMP-dependent protein kinase-stimulated phosphorylation was optimum at pH 6.8; phosphorylase b kinase phosphorylation had a biphasic curve in cardiac and slow skeletal muscle with optima at pH 6.8 and 8.0. The addition of exogenous phosphorylase b kinase or protein kinase increased the endogenous level of phosphorylation 25-100%. All sarcoplasmic reticulum preparations contained varying amounts of adenylate cyclase, phosphorylase b and a (b:a = 30.1), "debrancher" enzyme and glycogen (0.3 mg/mg protein), as well as varying amounts of protein kinase and phosphorylase b kinase which were responsible for a significant endogenous phosphorylation. Thus, the two phosphorylating enzymes stimulated calcium uptake in the sarcoplasmic reticulum of a variety of muscles possessing different physiologic characteristics and different responses to drugs. In addition, the phosphorylation catalyzed by these enzymes occurred at two different protein moieties which make physiologic interpretation of the role of phosphorylation difficult. While the role phosphorylation in these mechanisms is complex, the presence of a glycogenolytic enzyme system may be an important link in this phenomenon. The sarcoplasmic reticulum represents a new substrate for phosphorylase b kinase.

Animals↗
PubMed1975

Modification of ventricular fibrillation latency following coronary artery occlusion in the conscious pig.

Abrupt occlusion of the left anterior descending coronary artery was performed on 45 unanesthetized farm pigs in order to evaluate the relative effects on the latency to ventricular fibrillation (VFL) of 1) adaptation of the animals to the laboratory, and 2) beta-receptor blockade by propranolol. Compared to control values, VFL was greatly lengthened (i.e., VF delayed or prevented) by adaptation (P smaller than 0.01), was shortened by large (2 MG/KG) doses of racemic propranolol in unadapted animals (P smaller than 0.02), and was again increased while under the influence of the drug, by adaptation (P smaller than 0.051). Neither a lower (0.02 mg/kg) dose of racemic propranolol, 2 mg/kg of dextropropranolol, nor ventricular pacing to a higher heart rate had an effect on VFL. The results suggest that reduced psychological stress was very effective in retarding or preventing the onset of VF, that low doses of propranolol were ineffective, and that higher doses were deleterious in unadapted animals.

Adaptation, Physiological↗
PubMed1975

The nature of the transport adenosine triphosphatase-digitalis complex. VIII. The relationship between in vivo-formed (3-H-ouabain-Na+, K+-adenosine triphosphatase) complex and ouabain-induced positive inotropism.

Ouabain interaction with a possible pharmacologic receptor, Na+, K+-adenosine triphosphatase (Na+, K+-ATPase), has been assessed by continual perfusion of canine hearts with various concentrations of both unlabeled and 3-H-ouabain. A positive dose-related correlation between enzyme inhibition, increased contractile force and drug binding to the enzyme has been established. The complex formed between 3-H-oubain and Na+, K+-ATPase in vivo appears to have the same characteristics as that formed in vitro, suggesting that the nature of both complexes is the same. These data are consistent with the concept that Na+, K+-ATPase may be an important pharmacologic receptor for cardiac glycosides.

Adenosine Triphosphatases↗