Drugs online research references
Pharmacol Res. 1998 Feb;37(2):151-5.
The responsiveness of the endogenous inhibitor of cAMP-dependent protein kinase to isoproterenol after prolonged treatment with nifedipine.
Zalewska-Kaszubska J, Marczak G, Wejman I, Wiktorowska A.
Department of Pharmacodynamics, Medical University, Lodz, Poland.
In the present study the response of the type I inhibitor activity to isoproterenol was used as an indirect index both of cAMP generation and beta-adrenergic receptor reactivity. Our results suggest that nifedipine, after prolonged treatment, produces subsensitivity in beta-adrenergic transmission without changes in the basal level of cAMP. Administration of isoproterenol produced a dose-dependent decrease of the type I inhibitor activity (an endogenous inhibitor of cAMP-dependent protein kinase, Walsh inhibitor) in the frontal cortex and hippocampus of rats. Prolonged treatment with nifedipine (5 mg kg-1 i.p., twice daily, 21 days) did not change the basal activity of the type I inhibitor, but markedly reduced the response of the type I inhibitor activity to isoproterenol. In the treated animals a significant decrease of the type I inhibitor was seen when isoproterenol was used in much higher doses than in control rats.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9572071&dopt=Abstract
Cell Calcium. 1992 Nov;13(10):615-26.
Characterization of the energy-dependent, mating factor-activated Ca2+ influx in Saccharomyces cerevisiae.
Prasad KR, Rosoff PM.
Department of Pediatrics (Hematology/Oncology), Tufts University School of Medicine, Boston, Massachusetts.
The yeast mating pheromones, a and alpha factors, bind to specific G protein-coupled receptors in haploid cells and bring about both growth arrest in the early G1 phase of the cell cycle and differentiation into mating capable cells. This induces an increase in Ca2+ influx leading to elevated intracellular calcium concentrations, which has been shown to be essential for subsequent downstream events and the mating process itself [1]. We have characterized the alpha factor induced increase in cellular Ca2+ in wild type S. cerevisiae and in the temperature-sensitive cell division cycle mutants cdc7 and cdc28 which are growth-arrested at the G0-G1 border at the nonpermissive temperature. We observed a 2-4 fold increase in the initial velocity of Ca2+ influx in alpha factor-treated wild-type cells and in cdc7 and cdc28 cells grown at the nonpermissive temperature. Calcium influx was energy dependent, inhibited by membrane depolarization and slightly increased by hyperpolarization. Furthermore, Ca2+ influx was sensitive to both divalent and trivalent cations, but was unaffected by nifedipine and verapamil. These data demonstrate that budding yeast possesses a regulated Ca2+ transport mechanism, the activation of which is dependent upon exit out of the cell cycle and growth cessation. This transport mechanism has many similarities to that observed in mitogen-stimulated mammalian cells.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1337499&dopt=Abstract
Basic Res Cardiol. 1986;81 Suppl 1:79-94.
Some problems of cardiac energetics.
Siess M, Stieler K, Leuchtner J, Delabar U.
Special problems of the aerobic metabolism in the cardiac muscle cell as an energy producing and energy consuming system are discussed and demonstrated with some experimental results using superfused resting and working guinea-pig atria as an energetic model: 1. Influence on resting O2 uptake: a) Free fatty acids (FFA) increase the O2 uptake rate to approximately 20% compared with glucose oxidation. This can be explained as a compensating effect due to the 9.7% lower combustion value for 1 mol O2 of C16-FFA and the 10.7% lower P/O-ratio related to glucose oxidation. b) K+-depolarization increases the O2 uptake b.1. between 15 and 65 mmol/l KCl from 110 to 200% without activation of the actomyosin system. This effect is Ca++ dependent and is not observed in Ca++ free solution and can be inhibited completely by nifedipine. The enhanced O2 uptake rate due to K+-depolarization is not connected with an improved state of the energy quotient (ATP/ADP+AMP) indicating a lowering of the energy coupling. b.2. between 100 and 250 mmol/l KCl from 220 to approximately 350%, not influenced by nifedipine and connected with activation of the actomyosin system at low Na+ and/or high external Ca++ (contracture). 2. Stretching of resting atria up to 10 mN tension does not increase the O2 uptake rate. The 'Feng' effect could not be confirmed. 3. a) The 'Frank-Starling' effect can be observed between 2.5 and 10 mN preload with increase of contractile work/beat connected with an enhancement of O2 uptake rate to a lower percentage. At the maximum of the 'Frank-Starling' effect the highest efficiency of contractile work can be observed. With increasing beat rate this maximum is shifted to a lower preload. b) The auxotonic contractile work measured by a calibrated spring blade allows the calculation of the 'internal work' and the 'external contractile work'/beat in mm X mN. The total energy of the activated actomyosin system (total work) is stored by the displacement of the spring blade due to the constant of the spring blade, the preload (tension) and the afterload (force). The 'internal work' will be transformed into ATP dependent heat and force equal to the preload tension. The same ATP dependent energy from O2 uptake is transformed at the same beat rate and the same preload a) with the isometric type of auxotonic contraction into high force and very low internal and low external work.(ABSTRACT TRUNCATED AT 400 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3790047&dopt=Abstract
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