Central Actions of Benzodiazepines: General Introduction

1978 ◽  
Vol 133 (3) ◽  
pp. 231-238 ◽  
Author(s):  
W. E. Haefely
Keyword(s):  
Vestibular Nucleus ◽  
Benzodiazepine Receptor ◽  
Inhibitory Effect ◽  
Dorsal Column ◽  
Target Cells ◽  
Dorsal Column Nuclei ◽  
Psychotropic Effects ◽  
Central Actions ◽  
Benzodiazepine Binding Sites ◽  
Facilitatory Action

SummaryAfter a brief review of the characteristic somatic and psychotropic effects of benzodiazepines evidence is presented which supports a specific facilitatory action of these drugs on GABA ergic synapses within the mammalian central nervous system. Benzodiazepines enhance presynaptic inhibition in the spinal cord and dorsal column nuclei as well as postsynaptic inhibition in dorsal column nuclei, hippocampus, hypothalamus, cerebral cortex, cerebellar cortex, which are all examples of recurrent and collateral inhibition mediated by GABA ergic intrinsic neurones. In addition, the compounds also enhance the inhibitory effect of GABA ergic long projection neurones in the substantia nigra and the lateral vestibular nucleus of Deiters. Several problems remain to be solved, such as the exact site at which benzodiazepines initiate their action (pre-synaptically at GABA ergic nerve endings or postsynaptically at the target cells) and the possible existence of endogenous ligands for the benzodiazepine receptor. Some suspected implications which studies on benzodiazepine binding sites could have for a deeper understanding of the mode of action of these drugs are discussed.

scholarly journals Middle East Respiratory Syndrome Coronavirus Spike Protein Is Not Activated Directly by Cellular Furin during Viral Entry into Target Cells

2018 ◽  
Vol 92 (19) ◽  
Author(s):  
Shutoku Matsuyama ◽  
Kazuya Shirato ◽  
Miyuki Kawase ◽  
Yutaka Terada ◽  
Kengo Kawachi ◽  
...  
Keyword(s):  
Middle East ◽  
Viral Entry ◽  
Cathepsin L ◽  
Inhibitory Effect ◽  
Middle East Respiratory Syndrome ◽  
Cell Entry ◽  
Target Cells ◽  
Furin Cleavage ◽  
S Protein ◽  
Entry Assay

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes host cellular proteases to enter cells. A previous report shows that furin, which is distributed mainly in the Golgi apparatus and cycled to the cell surface and endosomes, proteolytically activates the MERS-CoV spike (S) protein following receptor binding to mediate fusion between the viral and cellular membranes. In this study, we reexamined furin usage by MERS-CoV using a real-time PCR-based virus cell entry assay after inhibition of cellular proteases. We found that the furin inhibitor dec-RVKR-CMK blocked entry of MERS-CoV harboring an S protein lacking furin cleavage sites; it even blocked entry into furin-deficient LoVo cells. In addition, dec-RVKR-CMK inhibited not only the enzymatic activity of furin but also those of cathepsin L, cathepsin B, trypsin, papain, and TMPRSS2. Furthermore, a virus cell entry assay and a cell-cell fusion assay provided no evidence that the S protein was activated by exogenous furin. Therefore, we conclude that furin does not play a role in entry of MERS-CoV into cells and that the inhibitory effect of dec-RVKR-CMK is specific for TMPRSS2 and cathepsin L rather than furin. IMPORTANCE Previous studies using the furin inhibitor dec-RVKR-CMK suggest that MERS-CoV utilizes a cellular protease, furin, to activate viral glycoproteins during cell entry. However, we found that dec-RVKR-CMK inhibits not only furin but also other proteases. Furthermore, we found no evidence that MERS-CoV uses furin. These findings suggest that previous studies in the virology field based on dec-RVKR-CMK should be reexamined carefully. Here we describe appropriate experiments that can be used to assess the effect of protease inhibitors on virus cell entry.

The ventroposterior inferior nucleus in the thalamus of cats: a relay nucleus in the Pacinian pathway to somatosensory cortex

1986 ◽  
Vol 56 (6) ◽  
pp. 1475-1497 ◽  
Author(s):  
P. Herron ◽  
R. Dykes
Keyword(s):  
Somatosensory Cortex ◽  
Dorsal Column ◽  
Lateral Part ◽  
Distinct Region ◽  
Cutaneous Mechanoreceptors ◽  
Dorsal Column Nuclei ◽  
Electrophysiological Recordings ◽  
Posterior Group ◽  
Relay Nucleus ◽  
Definition Of

The ventroposterior region of the thalamus of mongrel cats was searched to locate zones activated by somatic stimuli. By using stimuli that selectively excited Pacinian corpuscles, areas activated by this class of afferent fibers were differentiated from regions activated by other classes of cutaneous mechanoreceptors. The results showed that Pacinian inputs excite neurons in the ventroposterior inferior nucleus (VPI) of the thalamus, whereas other more dorsal zones within the ventroposterior thalamus receive inputs from other mechanoreceptor classes. This definition of the VPI tended to be larger and to extend further lateral than some published descriptions. Horseradish peroxidase (HRP) was injected into ventroposterior zones shown by electrophysiological recordings to receive inputs from Pacinian afferents. Subsequently, labeled cell bodies were observed in the caudal poles of the dorsal column nuclei, a region previously shown to be activated by Pacinian afferents. Very few labeled cells were found in the central region of these nuclei, a region previously shown to be activated by other classes of cutaneous mechanoreceptors. Electrophysiological recordings were used to locate a small portion of the second somatosensory cortex driven by Pacinian stimuli. When HRP was injected into this region cell bodies in the VPI and the lateral part of the posterior group were labeled, but few or no labeled cells were found in ventroposterior lateral nucleus. We hypothesize that the VPI receives Pacinian information from a cytoarchitecturally distinct region in the caudal poles of the dorsal column nuclei. Further, we suggest that a major cortical target for the VPI is a subdivision of the second somatosensory cortex. These studies do not exclude the possibility that Pacinian inputs have other thalamic and cortical targets.

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