Sheu L. Lee

β-endorphin concentration in the brain of intact and hypophysectomized rats

Abstract The brain concentration and distribution of β-endorphin immunoreactivity in the brain have been studied in intact and hypophysectomized rats. The results obtained with different methods for killing the animals and extracting β-endorphin are compared. Different methodologies of killing the rat and extracting the brain yield concentrations of β-endorphin which vary ten fold. Consistently the highest concentrations of β-endorphin have been found in the hypothalamus, midbrain and hindbrain. After hypophysectomy major reduction of β-endorphin concentration in the brain was observed.

Functional and subcellular changes in the isolated rat heart perfused with oxidized isoproterenol

Abstract The isolated rat heart failed to generate contractile force within 10, 15 and 60 min upon perfusion with medium containing 100, 50 and 20 mg/l oxidized isoproterenol respectively, whereas the contractile force was depressed by about 85% of control following a 90 min perfusion with 10 mg/l oxidized isoproterenol. Swelling of mitochondria and sarcoplasmic reticulum, and disruption of the contractile proteins were seen in all hearts failing due to oxidized isoproterenol. Furthermore, calcium uptake activity, but not calcium binding of the microsomal fraction from hearts perfused with oxidized isoproterenol was depressed, whereas mitochondrial calcium binding and uptake activities were unaffected. Perfusion of the hearts with oxidized isoproterenol did not change the mitochondrial or microsomal ATPase activities; however, mitochondrial phosphorylation rate, state 3 respiration and RCI values were significantly depressed. These results indicate changes in subcellular mechanisms during the induction of myocardial necrosis and contractile failure due to oxidized isoproterenol.

Effects of acebutolol, practolol and propranolol on the rat heart sarcolemma☆

Abstract The actions of acebutolol, practolol and propranolol on the rat heart sarcolemmal ATPase, adenylate cyclase and calcium binding activities were studied. None of these agents had any effect on the basal adenylate cyclase activity. Only propranolol at 2 mM or higher concentrations depressed calcium binding; this inhibitory effect was less pronounced at high concentrations of calcium. Propranolol (1–5 mM), but not practolol, markedly depressed Na+-K+ ATPase activity whereas acebutolol (3–5 mM) produced a slight but significant inhibition. Propranolol (1–5 mM), but not acebutolol or practolol, also inhibited the Ca2+ ATPase and Mg2+ ATPase activities. These results indicate sarcolemmal membrane as the site affected by propranolol and it is suggested that the cardiodepressant action of high doses of this agent may partly be due to changes in the sarcolemmal ATPase and calcium binding activities.

Abnormalities in heart membranes and myofibrils during bacterial infective cardiomyopathy in the rabbit.

We studied hearts from sham-operated and unin-fected catheterized rabbits as well as from rabbits at early and late stages of cardiomyopatny and failure after 3 and 6 days of infection with Streptococcus viridans. No ultrasrructural abnormalities or biochemical changes in membrane and myofibrillar activities were seen in 3-day uninfected hearts. ID 6-day uninfected hearts there were decreased sarcolemmal M>+ATPase, Na+-K+ ATPase, adenylate cydase and calcium binding, microsomal calcium binding and uptake, and myofibrillar Ca2+- stimulated ATPase as well as increased mitochondria! calcium uptake. Slight ultrastructural changes also were apparent in 6-day uninfected hearts. At both early and late stages of infective cardiomyopatfay and failure there were varying degrees of depression in sarcolemmal Mg2+ ATPase, Na+-K+ ATPase, adenylate cydase and calcium binding, microsomal calcium binding, calcium uptake and basal ATPase, and myofibrillar Ca2+-stimulated ATPase activities. However, sarcolemmal Ca2+ ATPase and myofibrillar Mg2+ ATPase activities were decreased only after 6 days of infection. Mitochondrial calcium binding and uptake were increased in early stages but decreased in late stages of disease. Furthermore in infected hearts there were defects in mito-chondrial respiration and pbosphorylation. Generalized severe royo-cardial cell damage involving myofibrils, mitochondria, and the sarcotubular system was seen only in late stages of infection. The results demonstrate impairment of different membrane and contractile protein functions as well as ultrastructural abnormalities in bacterial cardiomyopathic hearts which were absent or of lesser magnitude in hearts with only hypertrophy. The findings reported here suggest to us that there is an association between heart failure and changes in function of cellular components during bacterial infective cardiomyopathy.

Effects of chlorpromazine and imipramine on rat heart subcellular membranes

Abstract The effects of chlorpromazine and imipramine at concentrations ranging from 25 to 120 (μm on ATPase activities, as well as calcium binding and uptake abilities of the rat heart subcellular membranes, were studied in vitro . Chlorpromazine significantly decreased calcium binding. Mg 2+ ATPase and Na + −K + ATPase activities of the sarcolemmal fraction, whereas imipramine decreased calcium binding, Ca 2+ ATPase and Mg 2+ ATPase activities. Chlorpromazine also produced significant inhibition of the calcium binding and uptake abilities of the microsomal and mitochondrial fractions, while imipramine depressed the mitochondrial calcium uptake activity only at concentrations of 80 μm or higher. The mitochondrial respiratory and oxidative phosphorylation activities were depressed at high concentrations of these drugs. Since different membrane systems have been considered to be involved in the regulation of heart function and metabolism, the observed decreases in ATPase and calcium-accumulating activities of the heart subcellular membranes may represent one of the molecular mechanisms for the cardiodepressant actions of chlorpromazine and imipramine.

High K+-induced release of somatostatin from the cortical preparation of rat brain

Release of endogenous somatostatin (SRIF) from the rat cerebral cortical slices incubated in Krebs-bicarbonate buffer was increased from the basal rate of 3.4±0.6% of the total SRIF content in 15 min at [K+]o=5.6 mM, to 13.1±1.6% upon raising the [K+]o to 56.6 mM. The high-K+ evoked SRIF release was absent when Ca++ in the medium was replaced by Mn++. The isolated synaptosomes from rat cerebral cortex contain 13.2±3.1 ng SRIF/mg protein compared to 0.33±0.01 ng/mg protein in the cortical tissue as a whole, suggesting that nerve terminals are the main source of the peptide released upon membrane depolarization.

Ca2+-channels and adrenoceptors in diabetic skeletal muscle

The status of Ca(2+)-channels and adrenoceptors in the hind leg skeletal muscle was examined in rats 8 weeks after inducing diabetes by an intravenous injection of streptozotocin (65 mg/kg). Scatchard plot analysis of the data on specific binding of 3H-nitrendipine with crude membranes from diabetic muscle revealed an increase in the density of Ca(2+)-channels without any significant change in their affinity for the ligand. An increase in the density of beta-adrenoceptors without any alteration in their affinity, as measured by 3H-dihydroalprenolol binding, was also evident in the diabetic muscle. The observed increase in the number of Ca2+ channels or beta-adrenoceptors seems specific since no change in the alpha-adrenoceptor density or affinity, as measured by 3H-prazosin binding, was seen in the diabetic membranes. These results support the view that higher activities of Ca2+ transport systems or regulatory mechanisms may be associated with hyperfunction of the diabetic skeletal muscle.

Effects of some volatile anesthetic agents on rat heart sarcolemma

Abstract The effects of ether, chloroform and halothane on rat heart sarcolemmal ATP hydrolyzing and calcium binding activities were studied. Sarcolemmal Na + − K + ATPase activity was inhibited by halothane (1.8 – 18 mM) and stimulated by ether (7.1 – 42.6 mM) and chloroform (7.5 – 45 mM). Higher concentrations of ether (56.8 – 71 mM) and chloroform (60 – 75 mM) depressed the Na + − K + ATPase activity. Chloroform (7.5 – 75 mM) and halothane (1.8 – 18 mM) were found to decrease Mg 2+ ATPase and Ca 2+ ATPase activities, whereas e0her (42.6 – 71 mM) depressed only the Mg 2+ ATPase activity. Sarcolemmal calcium binding was depressed by ether (42.6 – 71 mM), chloroform (45 – 75 mM) and halothane (10.8 – 18 mM). These results suggest that the anesthetic - induced cardiac depression may partly be due to decreased sarcolemmal activities.