Noncontact dipole effects on channel permeation. III. Anomalous proton conductance effects in gramicidin

Proton transport on water wires, of interest for many problems in membrane biology, is analyzed in side-chain analogs of gramicidin A channels. In symmetrical 0.1 N HCl solutions, fluorination of channel Trp(11), Trp-(13), or Trp(15) side chains is found to inhibit proton transport, and replacement of one or more Trps with Phe enhances proton transport, the opposite of the effects on K(+) transport in lecithin bilayers. The current-voltage relations are superlinear, indicating that some membrane field-dependent process is rate limiting. The interfacial dipole effects are usually assumed to affect the rate of cation translocation across the channel. For proton conductance, however, water reorientation after proton translocation is anticipated to be rate limiting. We propose that the findings reported here are most readily interpreted as the result of dipole-dipole interactions between channel waters and polar side chains or lipid headgroups. In particular, if reorientation of the water column begins with the water nearest the channel exit, this hypothesis explains the negative impact of fluorination and the positive impact of headgroup dipole on proton conductance.     

5-HYDROXY-l-TRYPTOPHAN DECARBOXYLASE ACTIVITY: MICROASSAY AND DISTRIBUTION IN DISCRETE RAT BRAIN NUCLEI

Abstract— 5-Hydroxy- l -tryptophan decarboxylase (EC 4.1.1.28) activity was measured in discrete regions of the rat brain by means of a sensitive micromethod lhat allows the quantitation of enzyme activity in μg amounts of brain tissue.
A good correlation was obtained between serotonin levels and 5-hydroxy- l -tryptophan decarboxylase activity in all the brain regions examined. Wide differences in enzyme activity were found in the different brain nuclei, with a 20-fold difference in activity between the most active region (the nucleus raphe dorsalis) and the least active regions (the corpus callosum and the optic tract).     

Quantitative autoradiographic characterization of receptors for angiotensin II and other neuropeptides in individual brain nuclei and peripheral tissues from single rats

Autoradiographic techniques coupled with computerized microdensitometry and comparison with 125I standards were used to characterize and quantitate receptors for neuropeptides in rat brain and adrenal and pituitary glands. These techniques are rapidly performed, anatomically precise, and more sensitive than membrane binding techniques. They permit the determination of complete saturation curves and Scatchard analysis in discrete nuclei of the rat brain and in single rat pituitary and adrenal glands. Angiotensin II (AII) receptors were quantitated after incubation of 16-micron tissue sections with the AII agonist 125I-[Sar1]-AII. High-affinity, high-density AII receptors were present in the organon subfornicalis, organon vasculosum laminae terminalis and nuclei triangularis septalis, suprachiasmatis, and paraventricularis of the rat and in rat adrenal capsule-zona glomerulosa area, adrenal medulla, and anterior pituitary. These techniques could be used for precise localization and quantitation of other neuropeptide receptors in single rat brain nuclei, after optimizing the assay conditions and provided that suitable 125I ligands are available.     

Angiotensin and Cerebral Blood Flow

1.General properties of the cerebral circulation.2.Cerebral blood flow autoregulation in hypertension, in stroke, and during the aging process.3.The Angiotensin system.4.Angiotensin receptor subtypes.5.Angiotensin receptors and actions of Angiotensin II in the brain: interactions between the brain and circulating Angiotensin II.6.The cerebrovascular Angiotensin system.7.Effects of Angiotensin II on cerebrovascular reactivity.8.Angiotensin and cerebrovascular flow.9.Effects of therapeutic modulation of the Angiotensin II system on cerebrovascular regulation in health and disease.10.Conclusions.