A possible physiological basis for ocular dominance

An experiment is undertaken to investigate the relationship between "sighting" and motor dominance. A review of recent work on the neurophysiology of vision is carried out and an attempt to explain ocular dominance using this is made.     

A possible physiological basis for the dud-stud phenomenon

Intact male rats were tested on two successive weekly tests with females to determine their level of sexual activity. Nuclear estrogen receptor content was measured in specific brain regions of individual sexually responsive and sexually nonresponsive males. Sexually nonresponsive male rats had significantly reduced nuclear estrogen receptor levels in the preoptic area compared to sexually responsive males. Sexually active males did not differ from inactive males in nuclear estrogen receptors in the medialbasal hypothalamus.     

Local Anesthetics Affect Gramicidin A Channels via Membrane Electrostatic Potentials

The effects of local anesthetics (LAs), including aminoamides and aminoesters, on the characteristics of single gramicidin A (GA) channels in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers were studied. Aminoamides, namely lidocaine (LDC), prilocaine (PLC), mepivacaine (MPV), and bupivacaine (BPV), reduced the conductance of GA channels. Aminoesters influenced the current fluctuations induced by GA differently; procaine (PC) did not affect the fluctuations, whereas tetracaine (TTC) distinctly reduced the conductance of single GA channels. Using electrophysiological technique, we estimated the changes in the membrane boundary potential at the adsorption of LAs; LDC, PLC, MPV, BPV, and TTC substantially increased, while PC did not affect it. To elucidate which component of the membrane boundary potential, the surface or dipole potential, is responsible for the observed effects of LAs, we employed a fluorescence assay. We found that TTC led to a significant increase in the membrane dipole potential, whereas the adsorption of LDC, PLC, MPV, BPV, and PC did not produce any changes in the membrane dipole potential. We concluded that aminoamides affected the surface potential of lipid bilayers. Together, these data suggest that the effects of LAs on the conductance of single GA channels are caused by their influence on membrane electrostatic potentials; the regulation of GA pores by aminoamides is associated with the surface potential of membranes, whereas TTC modulation of channel properties is predominantly due to changes in dipole potential of lipid bilayers. These data might provide some significant implications for voltage-gated ion channels of cell membranes.     

Interaction of Serotonin1A Receptors from Bovine Hippocampus with Tertiary Amine Local Anesthetics

1. We have examined the interaction of tertiary amine local anesthetics with the bovine hippocampal serotonin1A (5-HT1A) receptor, an important member of the G-protein-coupled receptor superfamily. 2. The local anesthetics inhibit specific agonist and antagonist binding to the 5-HT1A receptor at a clinically relevant concentration range of the anesthetics. This is accompanied by a concomitant reduction in the binding affinity of the 5-HT1A receptor to the agonist. Interestingly, the extent of G-protein coupling of the receptor is reduced in the presence of the local anesthetics. 3. Fluorescence polarization measurements using depth-dependent fluorescent probes show that procaine and lidocaine do not show any significant change in membrane fluidity. On the other hand, tetracaine and dibucaine were found to alter fluidity of the membrane as indicated by a fluorescent probe which monitors the headgroup region of the membrane. 4. The local anesthetics showed inhibition of agonist binding to the 5-HT1A receptor in membranes depleted of cholesterol more or less to the same extent as that of control membranes in all cases. This suggests that the inhibition in ligand binding to the 5-HT1A receptor brought about by local anesthetics is independent of the membrane cholesterol content. 5. Our results on the effects of the local anesthetics on the ligand binding and G-protein coupling of the 5-HT1A receptor support the possibility that G-protein-coupled receptors could be involved in the action of local anesthetics.     

Regulation of the Pore-Forming Activity of Cecropin A by Local Anesthetics

The influence of local anesthetics on the regulation of the channel-forming activity of the antimicrobial peptide cecropin A has been investigated. The mean current flowing through the single cecropin channels i_sc was determined, and steady-state transmembrane current induced by cecropin AI_∞ was measured. It has been shown that the introduction of 1 mM of bupivacaine, benzocaine or 0.3 mM of tetracaine into the membrane bathing solution results in a decrease in i_sc and I_∞. At the same time, the addition of 1 mM lidocaine or procaine to the membrane-bathing solutions does not lead to a significant change in i_sc and I_∞. Comparison of the absolute values and the sign of the change in the boundary potential of negatively charged membranes and relative changes of i_sc and I_∞ after addition of local anesthetics shows that neither parameter correlates with the membrane boundary potential. The results of studying the effect of tested local anesthetics on the phase transition of membrane lipids allow us to conclude that the observed changes of i_sc and I_∞ are due to modulation of the elastic properties of the membrane.     

Acceleration of the Cleavage in Sea Urchin Eggs by Treatments with Local Anesthetics (II) Treatments with Some Other Local Anesthetics than Procaine*

Unfertilized sea urchin eggs were exposed to sea water solutions of local anesthetics, such as caffeine, tetracaine and ethyl urethane, and the herbicide, isopropyl N-phenyl carbamate (IPC) for 10min and returned to normal sea water. Then they were inseminated 5min later. When eggs were pre-treated with 1–2 mM caffeine, 0.02–0.05 mM tetracaine, 50–100 mM ethyl urethane and 2% saturated sea water of IPC, respectively, they could cleave and hatch earlier than the control eggs. However, when fertilized eggs were continuously post-treated with solutions of the agents except IPC at the same concentrations as those in the case of the pre-treatments, the fertilized eggs could not cleave or were retarded in development. The possible mechanisms of the cleavage acceleration by pre-treatments with local anesthetics were discussed.     

A possible basis for major histocompatibility complex-restricted T-cell recognition

Four distinct T-cell antigen-receptor gene loci have now been identified and partly characterized: alpha, beta, gamma and delta. All of these loci can rearrange in an immunoglobulin-like fashion and express polypeptides that contribute to either alpha:beta or gamma:delta T-cell receptor-CD3 complexes. Surprisingly, the T-cell receptor (TCR) delta coding regions are located entirely, or almost entirely, within the TCR alpha locus and share at least some of the V region gene segments, thus at least partly linking the two different types of receptor heterodimers. Analysis of potential T-cell receptor diversity, particularly that of the delta chain, indicates a striking concentration of somatic polymorphism in the V-J junctional region of the two heterodimers, four to six orders of magnitude higher than similar calculations for immunoglobulin light- and heavy-chain combinations. In contrast, the number of possible V region combinations in T-cell receptors is one hundredth to one thousandth that of immunoglobulins. TCR alpha: beta heterodimers are known to recognize many possible fragments of antigens embedded in the peptide-binding clefts of a relatively small number of major histocompatibility complex (MHC) molecules. Thus it is attractive to speculate that the V-J junctional portions of both types of T-cell receptor contact peptide antigens, whereas the remaining diversity regions contact the MHC. This contention is supported by molecular modelling studies and has interesting implications for the evolution of antigen-receptor genes.     

Local effect for [5-3H]cytosine decays: Production of a chemical product with possible mutagenic consequences

Purified bacterial DNA containing [2-¹⁴C, 5-³H]cytosine was stored at ?196 °C to accumulate tritium decays. At various storage times samples were analyzed by two-dimensional thin-layer chromatography, following hydrolysis of the DNA. The major product detected as a function of an increasing number of tritium decays was uracil, which was formed with an efficiency of 28% per tritium decay. Uracil possesses the genetic coding properties of thymine and, therefore, would account for the high efficiency of C → T transitions previously reported in mutagenesis studies employing [5-³H]cytosine. A possible reaction mechanism leading to the formation of uracil from [5-³H]cytosine decay is presented.     

Phospholipids as components of the nuclear matrix: their possible biological significance

The phospholipid involvement in the regulation of the functional and structural properties of the nuclear matrix is discussed analysing the results obtained with the enzymic removal of these molecules. Namely phospholipids seem to mediate hydrophobic interactions between nucleic acids and matrix fibrils either directly or indirectly through an association with the non-histone proteins of the matrix.     

Effect of Local and General Anesthetics on Interfacial Water

BackgroundWater undergoes structural change as it interfaces with hydrophilic surfaces, including the many hydrophilic surfaces within the cell. This interfacial water has become known as “Exclusion Zone (EZ) water” or “fourth-phase water” [1].MethodsWe tested the hypothesis that anesthetics diminish the amount of EZ water, and that this change may correlate with functional changes in anesthesia. By using the local anesthetics Lidocaine and Bupivacaine as well as a general inhalational anesthetic, Isoflurane, we tracked the EZ size as these anesthetics were introduced.ResultsAll three anesthetics diminished EZ size in a concentration-dependent manner at concentrations of 0.18 mM and greater for Bupivacaine, 0.85 mM and greater for Lidocaine, and 0.2% for Isoflurane. At extremely low (micromolar) concentrations, however, all three anesthetics increased EZ size.ConclusionsThe sharp increase of EZ size associated with micromolar anesthetic concentrations follows a similar pattern to induction of general anesthesia, from the excitation stage (Stage II) to the depression and overdose stages of surgical anesthesia (Stages III and IV). The results are consistent with the hypothesis that anesthetics may act on water, a fundamental organizational component common to all cells.