Biomedical subjects
Publications and source records attributed to S Gitter.
The activity of dopamine-beta-hydroxylase was measured in the serum before and immediately after electroconvulsive treatments. No significant difference was observed, suggesting that the seizures did not cause an increase in the peripheral sympathetic tone.
Dopamine-beta-hydroxylase activity was measured in serum samples that were incubated at 37 degrees C for up to seven days and were compared with preincubation values. No change of activity was observed.
The activity of dopamine beta-hydroxylase in the serum was measured in patients with acute cardiac disorders who were admitted to a coronary care unit. The activity of the enzyme on admission was similar in patients with acute myocardial infarction and in those with other conditions; on discharge, the activity was reduced significantly. Patients with myocardial infarction had the greatest fall in the activity of dopamine beta-hydroxylase. Patients with multiple signs of sympathetic hyperactivity had significantly higher values for the activity of dopamine beta-hydroxylase on admission. Pain was found to significantly increase the activity of the enzyme. These data confirm findings that the activity of dopamine beta-hydroxylase in the serum reflects the intensity of sympathetic activity. The factors contributing to the elevated sympathetic activity in some patients with acute myocardial infarction seem to be nonspecific, but because of the ominous nature of increased sympathetic tone in this condition, it could be advantageous to identify these patients.
A new compound, AF3 (4-ethyl-6-oxa-1-azatricyclo)4.2.2.02,7)dodecan-5-one), and its 4-phenyl analogue, AF6, embodying the structural elements of acetylcholine in a highly rigid framework, were shown to evoke nicotine-like responses in the nictitating membrane (NM) and blood pressure when applied to the superior cervical ganglion in anaesthetized cats. In this respect, their equiactive molar ratio was (nicotine : 1),20-30. However, at doses that were too low to evoke any response, AF3 appeared to potentiate the responses to nicotine or tetra-methylammonium (TMA) by preventing or abolishing tachyphylaxis to the two latter drugs, the effect being dose-dependent with AF3. DMPP which produces much less tachyphylaxis, or preganglionic nerve stimulation, was little or not potentiated in presence of AF3. It is proposed that potentiation to nicotine or TMA occurs following occupancy by AF3 of a regulatory subsite, thereby preventing further access to it by nicotine or TMA. In this respect, AF3 plays the role of a "neutral" molecule.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The QT interval has been studied in ECG in mouse and rat embryos during two stages of development. The QT interval during the early stage of development is prolonged and an ST segment clearly exists. Both disappear during fetal development and do not exist in adult animals in which the T wave immediately follows the QRS. Mammalian embryos have therefore been proposed as a model for the study of QT prolongation. It is suggested that the origin of the QT prolongation in the young embryos is caused by the prolonged duration of the action potentials of the primordial cardiac tissue. During embryonic development this tissue becomes organized as a conductive system surrounded by "neomyocardial" tissue with a shorter duration of action potential, which causes the shorter QT interval at this stage. Our working hypothesis is that the pathogenesis of the prolonged QT syndrome in children could be interpreted as an incomplete or delayed differentiation between the primordial or primordial-like myocardium retaining prolonged action potential duration, and "neomyocardium" with short duration.
The title compound (MSDQ) is a new muscarinic agonist related to 3-acetoxyquinuclidine (3-AcQ) but also of a highly rigid structure. In view of this, it may constitute a probe for the detection of heterogeneity among muscarinic receptors. Indeed, equipotent molar ratios (EPMR) for ACh, 3-AcQ and MSDQ were as follows: guinea pig ileum, 1 : 14 : 240; vasodepressor effect in the cat, 1 : 6 : 188. But EPMR for 3-AcQ and MSDQ as stimulants of the superior cervical ganglion in the cat were 1 : 1 and for the induction of tremors in mice, 9 : 5. No such subtle differences in receptor specificity were detected when the probe used was the 2, 2-diphenyl analogue (DiPSDQ) of MSDQ which was a powerful competitive antagonist in all systems, more potent than atropine, but with a CNS/PNS activity of 1.1 compared to 26 for atropine. In view of this, the use of potent antagonists as probes for muscarinic receptor heterogeneity is questionable.
A study of heterogeneity among muscarinic receptors was carried out with new rigid molecules, comprising structures in the fused quinuclidine-valerolactone, quinuclidine-cyclohexenone, quinuclidine-cyclohexanone and quinuclidine-cyclohexane derivatives. These are structurally related to the potent muscarinic agent, 3-acetoxyquinuclidine but substantially different from in it conformation. All proved to antagonize acetylcholine-like activity, but to a different extent in different systems. The equipotent molar ratio with respect to atropine (as 1) was: isolated guinea pig ileum, 10,000-1,000; salivary gland (mouse), 1,000-100; superior cervical ganglion (cat), 100-10; CNS (mouse), approximately 10. It is suggested that the rigid structure induces a three-point constrained fit in the receptor (onium group, hydrophobic moiety and carbonyl group), but that not all muscarinic receptors are capable of responding equally. In this case, receptor specificity of the drug is a direct consequence of its graded departure from the preferred conformation of acetycholine and, therefore, is necessarily associated with partial loss of potency.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.