Effect of beta-Adrenoceptor Antagonists on Phospholipid N-Methylation Activities of Cardiac Sarcolemma

BACKGROUND: Some beta-adrenoceptor antagonists exert a negative inotropic action by affecting Ca(2+) fluxes in the myocardial cell as a consequence of their interaction with sarcolemmal and sarcoplasmic reticular membranes. This action may be caused by their effects on the chemicophysical properties of membranes phospholipids. Because phosphatidylethanolamine (PE) N-methylation can influence the chemicophysical properties of membranes, these agents may affect PE N-methylation. This study was undertaken to examine the effects of propranolol, acebutolol, and atenolol on PE-N-methylation in rat heart sarcolemma (SL). METHODS AND RESULTS: Sarcolemmal membrane was isolated from rat hearts by the hypotonic shock LiBr method. Incorporation of radiolabeled methyl groups from S-adenosyl-l-methionine was assayed at three catalytic sites involved in the PE N-methylation reaction in the presence and absence of these drugs. A biphasic effect of propranolol at site I was noted; low concentrations (10(-8) M) were inhibitor. Acebutolol (10(-9)-10(-3) M) depressed methyl group incorporation in SL at site II in a dose-dependent manner, whereas atenolol showed no effect. Propranolol also exerted a biphasic effect on sarcoplasmic reticular (SR) methylation at site I, whereas acebutolol depressed the SR enzyme activity at site II and atenolol had no effect. The mitochondrial methyltransferase activities at sites I, II, and III were unaltered by any of these drugs. CONCLUSIONS: It is suggested that propranolol and acebutolol alter SL and SR PE N-methyltransferase activity at site I and site II, respectively, either by affecting the enzyme directly or by changing the physiochemical properties of the membrane.     

Sarcolemmal Na+-K+-ATPase activity in diabetic rat heart

Heart sarcolemmal membranes were isolated by the hypotonic shock-LiBr treatment from rats with chronic diabetes induced by a streptozotocin (65 mg/kg, iv) injection. Sarcolemmal Mg2+-dependent ATPase activity was elevated, whereas 5'-nucleotidase and K+-p-nitrophenylphosphatase activities in diabetic heart were depressed in comparison to control preparations. Although patent Na+-K+-ATPase and patent ouabain-sensitive Na+-K+-ATPase activities were unaltered, latent Na+-K+-ATPase activities, as determined in membranes after alamethicin or deoxycholate treatments, were found to be significantly depressed in diabetic animals. A depression in the latent Na+-K+-ATPase activity in diabetic preparations was also observed in membranes prepared by the sucrose density gradient method. Insulin-treated diabetic rats were observed to have normalized latent Na+-K+-ATPase activities. Total phospholipid content did not differ, but cholesterol content of the sarcolemmal membranes was significantly increased in diabetic heart preparations. Sarcolemmal Na+-K+-ATPase activity in diabetic heart was more resistant to treatments with filipin, an agent known to bind with cholesterol residues. These results suggest that chronic experimental diabetes is associated with some defects in sarcolemmal enzymatic activities and composition.     

Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy

The effects of insulin and thyroid hormone treatments on cardiac sarcoplasmic reticular function were investigated in chronic streptozotocin-induced diabetes in rats. ATP-dependent Ca2+ transport and Ca2+-stimulated ATPase activities were depressed significantly in microsomal samples from diabetic rats in comparison with control (P less than 0.05). This defect was seen at various times of incubation (1-20 min) and different concentrations of free Ca2+ (10(-7) to 10(-5) M Ca2+) and was accompanied by changes in the protein composition and phospholipid contents of the microsomal fraction. The defect in calcium transport in microsomal vesicles was not evident until 28 days after streptozotocin (65 mg/kg iv) injection, whereas increases in plasma glucose levels due to insulin-deficiency occurred within 3 days. All changes in function and composition of the sarcoplasmic reticulum were reversed by insulin administration to the diabetic rats. Although the plasma level of thyroid hormone was decreased in the diabetic rat, thyroid hormone treatment did not restore microsomal calcium transport in the diabetic animals. The results of this study provide some evidence that the depression in cardiac sarcoplasmic reticular calcium accumulation during diabetes is a consequence of insulin deficiency and associated chronic metabolic changes but the hypothyroid condition that accompanies experimental diabetes does not appear to play any role in this defect.     

Possible role of sarcolemmal Ca2+/Mg2+ ATPase in heart function

The Ca2+/Mg2+ ATPase, which is activated by millimolar concentrations of Ca2+ or Mg2+, has been found to exist in the heart sarcolemmal membrane. Although a great deal of work has been carried out to characterize the enzyme activity as well as to purify the enzyme, the physiological function of the enzyme remains to be elucidated. This enzyme has been shown to be different from other known ion transport ATPases such as Na(+)-K+ ATPase and Ca2(+)-stimulated ATPase in terms of the activation kinetics of various cations, the sensitivity towards specific inhibitors, and the molecular weights. In view of the existing data and circumstantial evidence, it has been proposed that the Ca2+/Mg2+ ATPase is involved in the entry of Ca2+ into the cardiac cells, the transport of Mg2+ across the cell membrane, and extracellular ATP signal transduction.     

Defective membrane systems in dystrophic skeletal muscle of the UM-X7.1 strain of genetically myopathic hamster.

1. The function of mitochondria, sarcotubular membranes (heavy microsomes), sarcolemma and myofibrils from the hind-leg skeletal muscle of about 60- and 150-day-old normal and myopathic (UM-X7.1) hamsters was examined. 2. The mitochondrial calcium uptake as well as mitochondrial phosphorylation and respiratory rates were lower in 60-day-old myopathic skeletal muscle, unlike 150-day-old myopathic animals, when pyruvate-malate and glutamate-malate were used as substrates. However, mitochondria from 150-day-old myopathic animals showed depressed glutamate-dependent respiratory and phosphorylation rates and succinate-supported initial rate of calcium uptake. 3. The microsomal calcium-uptake, but not calcium-binding, and Ca2+-stimulated adenosine triphosphatase (ATPase) activity of the 150-day-old myopathic skeletal muscle were lower than the control values. Although microsomal calcium-binding, calcium-uptake and ATPase activities of the 60-day-old myopathic muscle were not depressed significantly, the initial rate of calcium uptake was less than the control. 4. The sarcolemmal Ca2+-ATPase, but not Mg2+-ATPase or Na+ +K+-ATPase, activity was higher in 60-day-old myopathic muscle whereas the activities of all these enzymes from 150-day-old myopathic animals were higher than the control. On the other hand, the Na+ +K+-ATPase activities from 60- and 150-day-old myopathic animals were inhibited by ouabain to a lesser extent in comparison with the respective control values. 5. The myofibrillar Ca2+-ATPase and Mg2+-ATPase activities as well as inhibition of Mg2+-ATPase due to Na+ and K+ in myopathic muscle were no different from the control values. 6. The results reported here give further support to the view that different membrane systems of the dystrophic muscle are defective.     

Unusual presentation of mandibular extraoral sinus in a fourteen year old girl: a case report

A case of fourteen year old healthy girl with complaint of a discharging sinus on the lower right side of face is reported. All teeth were vital and there was no evidence of periodontitis. There was no history of extraction of a tooth. Total leucocyte count, differential leucocyte count, fasting blood sugar, chest x-ray and routine urine examination were within normal limits. Actinomycosis and scrofuloderma which simulate such a condition were ruled out by culture study. The intraoral periapical x-ray of mandibular molar showed questionable periapical changes at the time of presentation. But definite osteolysis was observed in the repeat radiograph after three months. It was decided to extract the second molar and curette the sinus tract. The extraction proved to be difficult. On examination of the extracted tooth, it was found that the mandibular second molar and second premolar were fused together. The radiograph of the tooth taken after extraction showed confluence of the premolar pulp with the periodontal membrane. On follow up, the lesion was found to heal satisfactorily.