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(-)-Pindolol, one of the most potent beta-adrenergic receptor antagonists, was radioiodinated using chloramine-T oxidation of carrier-free Na 125I and separated from unreacted pindolol to yield 2200 Ci/mmole (-)-[125I]-iodopindolol ((-)-[125I]-IPin). Mass and ultraviolet spectra confirmed that the iodination occurred on the indole ring, presumably at the 3(More)
In mouse right ventricular strips, field-stimulated to contract isometrically in an oxygenated bicarbonate-buffered physiological salt solution at 22--24 degrees C, isoproterenol (3 microM) stimulation of phosphorylase a accumulation was approximately a linear function of the rate of contraction from 0.2 to 5 Hz. In muscles incubated in the absence of(More)
In mouse right ventricular strips, field-stimulated to contract isometrically in an oxygenated bicarbonate-buffered physiological salt solution at 22--24 degrees C, the EC50 for the inotropic action of isoproterenol decreased from 37 nM in muscles stimulated at 0.2 Hz to 5 nM in muscles stimulated at 3.3 Hz. At higher rates of contraction, there was also an(More)
Forskolin directly stimulates adenylate cyclase activity and acts synergistically with receptor-mediated agonists which stimulate cyclic AMP production. We have previously observed that a 3-hr incubation of C6-2B rat astrocytoma cells with 6 nM cholera toxin in the presence of 1 microM forskolin results in cyclic AMP accumulation 9-fold greater than in the(More)
Inhibiting protein synthesis by incubating C6-2B rat astrocytoma cells with cycloheximide or emetine for periods up to 24 hours caused a progressive decrease in the accumulation of adenosine 3',5'-monophosphate (cyclic AMP) when the cells were challenged for 30 minutes with 100 microM forskolin. In contrast, cholera toxin-stimulated (6 nM, 3 hours) cyclic(More)
We have examined the roles that cyclic AMP and protein synthesis play in the development of refractoriness in C6-2B rat glioma cells using the diterpene, forskolin, a general activator of cyclic AMP-generating systems. Forskolin-stimulated cyclic AMP accumulation peaked at 30 min and declined thereafter to 10% of peak levels by 3 hr despite the continued(More)
Forskolin activates a variety of adenylate cyclase systems and acts synergistically with receptor-mediated agonists which stimulate cyclic AMP production. The mechanism(s) and site(s) of forskolin action remain unclear. In C6-2B rat astrocytoma cells, forskolin stimulated greater than a 100-fold increase in cellular cyclic AMP content with a half-maximally(More)
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