Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Small molecules present during brain tissue homogenization are known to be entrapped within subsequently isolated synaptosomes. We have revisited this technique in view of its systematic utilization to incorporate into nerve endings impermeant probes of large size. Rat neocortical synaptosomes were prepared in the absence or in the presence of each of the following compounds: 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), tetanus toxin (TeTx) or its light chain (TeTx-LC), pertussis toxin (PTx), anti-syntaxin, or anti-SNAP25 monoclonal antibodies. Release of endogenous GABA and glutamate was then evoked by high K+ depolarization. GABA and glutamate overflows were inhibited by entrapped BAPTA and in synaptosomes prepared by homogenization in the presence of varying concentrations of TeTx or TeTx-LC. When synaptobrevin cleavage in synaptosomes entrapped with TeTx was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by western blotting, the extent of proteolysis was found to correspond quantitatively to that of release inhibition. GABA and glutamate overflows were increased by entrapped PTx; moreover, (-)-baclofen inhibited amino acid overflow more potently in standard than in PTx-containing synaptosomes. The overflows of GABA and glutamate were similarly decreased following incorporation of anti-syntaxin or anti-SNAP25 antibodies. Synaptosomal entrapping may be routinely used to internalize membrane-impermeant agents of different size in studies of presynaptic mechanisms.
 ...
PMID:Entrapping of impermeant probes of different size into nonpermeabilized synaptosomes as a method to study presynaptic mechanisms. 1061 48

Concentrations of amino acids such as glutamate(Glu), glutamine(Gln), gamma-aminobutyric (GABA), glycerin(Gly) in rat cerebral cortex were measured by o-phthaldialdehyde method to clarify alterations of these amino acids in infectious brain injuries(IBI). The results were that Gln and GABA in groups treated by bordetella pertussis suspension(BP) 4h were increased compared to those in the group treated by the normal saline(NS) or the operative control(OC) and a positive correlation with water content or Evans blue content, respectively. In the 24h BP group, Gln was still increased; GABA and Gly were decreased compared to those in the NS or OC group. The findings suggest that GLu, Gln, and Gly play an important role and GABA may be a marker of injury in pathogenetic mechanism of IBI induced by BP.
 ...
PMID:[Alterations of amino acids in rat cerebral cortex of infectious brain injuries]. 1068 51

Kainate receptors are ionotropic receptors, also reported to couple to G(i)/G(o) proteins, increasing neuronal excitability through disinhibition of neuronal circuits. We directly tested in hippocampal synaptosomes if kainate receptor-mediated inhibition of GABA release involved a metabotropic action. The kainate analogue, domoate (3 microM), inhibited by 24% [(3)H]GABA-evoked release, an effect reduced by 76% in synaptosomes pre-treated with pertussis toxin. Protein kinase C inhibition attenuated by 82% domoate-induced inhibition of GABA release whereas protein kinase C activation did not change kainate receptor binding. Thus, domoate inhibition of GABA release recruits G(i)/G(o) proteins and a protein kinase C pathway.
 ...
PMID:Pertussis toxin prevents presynaptic inhibition by kainate receptors of rat hippocampal [(3)H]GABA release. 1071 63

Neuronal GABA(B) receptors regulate calcium and potassium currents via G-protein-coupled mechanisms and play a critical role in long-term inhibition of synaptic transmission in the CNS. Recent studies have demonstrated that assembly of GABA(B) receptor GABA(B)R1 and GABA(B)R2 subunits into functional heterodimers is required for coupling to potassium channels in heterologous systems. However whether heterodimerization is required for the coupling of GABA(B) receptors to effector systems in neurons remains to be established. To address this issue, we have studied the coupling of recombinant GABA(B) receptors to endogenous Ca(2+) channels in superior cervical ganglion (SCG) neurons using nuclear microinjection to introduce both sense and antisense expression constructs. Patch-clamp recording from neurons injected with both GABA(B)R1a/1b and GABA(B)R2 cDNAs or with GABA(B)R2 alone produced marked baclofen-mediated inhibition of Ca(2+) channel currents via a pertussis toxin-sensitive mechanism. The actions of baclofen were blocked by CGP62349, a specific GABA(B) antagonist, and were voltage dependent. Interestingly, SCGs were found to express abundantly GABA(B)R1 but not GABA(B)R2 at the protein level. To determine whether heterodimerization of GABA(B)R1 and GABA(B)R2 subunits was required for Ca(2+) inhibition, the GABA(B)R2 expression construct was microinjected with a GABA(B)R1 antisense construct. This resulted in a dramatic decrease in the levels of the endogenous GABA(B)R1 protein and a marked reduction in the inhibitory effects of baclofen on Ca(2+) currents. Therefore our results suggest that in neurons heteromeric assemblies of GABA(B)R1 and GABA(B)R2 are essential to mediate GABAergic inhibition of Ca(2+) channel currents.
 ...
PMID:Heteromeric assembly of GABA(B)R1 and GABA(B)R2 receptor subunits inhibits Ca(2+) current in sympathetic neurons. 1075 39

Presynaptic inhibition exerted by the common inhibitor on the closer and opener muscles and by the specific inhibitor on the opener muscle was investigated in the crab Eriphia spinifrons. In the closer muscle, activation of GABA(B) receptors by baclofen reduced the mean quantal content of excitatory junctional currents by about 25%. Blocking GABA(B) receptors with CGP 55845 diminished presynaptic inhibition at a similar percentage. GABA(B) receptor-mediated presynaptic inhibition is linked to G proteins. Application of pertussis toxin eliminated about 25% of the inhibition exerted by the common inhibitory neuron. GABA(B) receptors participate in presynaptic inhibition at release boutons of the slow and the fast closer excitor at a similar percentage. In the opener muscle, presynaptic inhibition of transmitter release from the same endings of the opener excitor was about 15% stronger with the specific inhibitor than with the common inhibitor. About 10% of the presynaptic inhibition produced by either one of the two inhibitors could be abolished by blocking GABA(B) receptors. The amplitudes of the excitatory junctional currents in the opener were reduced in the presence of baclofen by about 25%, suggesting that synaptic terminals of the opener excitor are endowed with a similar percentage of GABA(B) receptors as terminals of the slow and the fast closer excitors. Baclofen had no effect on postsynaptic inhibition, indicating that GABA(B) receptors are not involved in postsynaptic neuromuscular inhibition.
 ...
PMID:Presynaptic inhibition and the participation of GABA(B) receptors at neuromuscular junctions of the crab Eriphia spinifrons. 1075 44

Inwardly rectifying potassium (K(+)) channels gated by G proteins (Kir3.x family) are widely distributed in neuronal, atrial, and endocrine tissues and play key roles in generating late inhibitory postsynaptic potentials, slowing the heart rate and modulating hormone release. They are directly activated by G(betagamma) subunits released from G protein heterotrimers of the G(i/o) family upon appropriate receptor stimulation. Here we examine the role of isoforms of pertussis toxin (PTx)-sensitive G protein alpha subunits (G(ialpha1-3) and G(oalphaA)) in mediating coupling between various receptor systems (A(1), alpha(2A), D(2S), M(4), GABA(B)1a+2, and GABA(B)1b+2) and the cloned counterpart of the neuronal channel (Kir3.1+3.2A). The expression of mutant PTx-resistant G(i/oalpha) subunits in PTx-treated HEK293 cells stably expressing Kir3.1+3.2A allows us to selectively investigate that coupling. We find that, for those receptors (A(1), alpha(2A)) known to interact with all isoforms, G(ialpha1-3) and G(oalphaA) can all support a significant degree of coupling to Kir3.1+3.2A. The M(4) receptor appears to preferentially couple to G(ialpha2) while another group of receptors (D(2S), GABA(B)1a+2, GABA(B)1b+2) activates the channel predominantly through G(betagamma) liberated from G(oA) heterotrimers. Interestingly, we have also found a distinct difference in G protein coupling between the two splice variants of GABA(B)1. Our data reveal selective pathways of receptor activation through different G(i/oalpha) isoforms for stimulation of the G protein-gated inwardly rectifying K(+) channel.
 ...
PMID:The role of members of the pertussis toxin-sensitive family of G proteins in coupling receptors to the activation of the G protein-gated inwardly rectifying potassium channel. 1077 50

This study used whole cell patch clamp recordings in rat hypothalamic slice preparations to evaluate the effects of GABA(B) receptor activation on GABA(A)-mediated inhibitory postsynaptic currents (IPSCs) in paraventricular nucleus magnocellular neurons evoked by electrical stimulation in the suprachiasmatic nucleus (SCN). Baclofen induced a dose-dependent (1-10 microM) and reversible reduction in SCN-evoked IPSC amplitude (11/11 cells), blockable with 2-hydroxysaclofen (300 microM; 3/3 cells). IPSCs displayed paired-pulse depression (PPD), attenuated by both baclofen and 2-hydroxysaclofen, but neither altered resting membrane conductances or IPSC time constants of decay. Baclofen induced a significant dose-dependent (1-100 microM) reduction in frequency, but not amplitude, of spontaneous IPSCs and miniature IPSCs, reversible with 2-hydroxysaclofen pretreatment. Baclofen effects and PPD persisted in slices pretreated with pertussis toxin (PTX) and N-ethylmaleimide, implying that these GABA(B) receptors are coupled to PTX-insensitive G proteins. Responses were unaltered by barium (2 mM) or nimodipine, ruling out involvement of K(+) channels and L-type Ca(2+) channels. Thus pre- and postsynaptic GABA(B) and GABA(A) receptors participate in SCN entrainment of paraventricular neurosecretory neurons.
 ...
PMID:GABA(B) presynaptically modulates suprachiasmatic input to hypothalamic paraventricular magnocellular neurons. 1080 Dec 89

Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) are two recently identified neuropeptides with opposing effects on several CNS functions, including spinal nociception. The cellular mechanisms that underlie this antagonism are not known. Here, we have investigated the effects of both peptides on synaptic transmission mediated by the three fast neurotransmitters l-glutamate, glycine, and GABA in the superficial layers of the rat spinal cord horn, which constitute the first important site of integration of nociceptive information in the pain pathway. NST selectively reduced transmitter release from inhibitory interneurons via a presynaptic Bordetella pertussis toxin-sensitive mechanism but left excitatory glutamatergic transmission unaffected. In contrast, N/OFQ only inhibited excitatory transmission. In the rat formalin test, an animal model of tonic pain in which N/OFQ exerts antinociceptive activity, NST induced profound hyperalgesia after intrathecal application. Similar to glycine and GABA(A) receptor antagonists, NST had no significant effects in the rat tail-flick test, a model of acute thermal pain. Our results provide a cellular basis for the antagonism of N/OFQ and NST and suggest the existence of a so far unidentified membrane receptor for NST. In addition, they support a role of NST as an endogenous inhibitor of glycinergic and GABAergic neurotransmission in the sensory part of the spinal cord and as a mediator of spinal hyperalgesia.
 ...
PMID:Selective suppression of inhibitory synaptic transmission by nocistatin in the rat spinal cord dorsal horn. 1086 50

Experiments were designed to characterize the effect of progesterone and the zona pellucida (ZP) on the goat sperm acrosome reaction (AR) through a comparative study. Goat spermatozoa were incubated for 4h in Krebs-Ringer bicarbonate media (KRB) for capacitation. Progesterone and ZP stimulated exocytosis of capacitated spermatozoa in a dose-dependent manner. EGTA and La(3+), added 10min before the addition of the agonists, completely abolished the stimulatory effects. Ca(2+) influx was observed to occur through a calcium phosphate transporter. Picrotoxin and bicuculline, two GABA(A)/Cl(-) channel antagonists, also inhibited progesterone-induced AR when added 10min before steroid addition. ZP-induced AR was unaffected by these antagonists. Studies using pertussis toxin (PTX) showed that, unlike ZP, progesterone acts without the involvement of a G-protein. Progesterone-3-(O-carboxymethyl) oxime: BSA conjugate (P-BSA) also induced AR in capacitated sperm suspension. Results suggest that progesterone and ZP induce AR via specific membrane receptors through different mechanisms, both requiring an influx of Ca(2+). It is assumed that both the mechanisms reconcile at some stages of the cascade and elicits a similar physiological response.
 ...
PMID:Caprine sperm acrosome reaction: promotion by progesterone and homologous zona pellucida. 1086 26

Nystatin-perforated patch recordings were made from mechanically dissociated neurons (in which functional native presynaptic nerve terminals are preserved), isolated from the basolateral amygdala regions to investigate the effects of tandospirone on gamma-aminobutyric acidergic (GABAergic) inhibition. Two types of neurons, ovoid-shaped and pyramidal-shaped neurons, were obtained from the basolateral amygdala nuclei and the electrophysiological characteristics of these two types of neurons supported the morphological classification of these isolated neurons. From the ovoid-shaped neurons, bicuculline-sensitive GABA(A)ergic miniature inhibitory postsynaptic currents (miniature IPSC) were recorded in the presence of tetrodotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphovaleric acid (DL-AP5). Tandospirone (10 microM) reversibly and continuously inhibited the GABAergic miniature synaptic events to 66.3+/-2.1% of control (P<0.01, n=17) without affecting the miniature IPSC amplitude (104.0+/-3.1% of control, n=17). The similar inhibition of miniature IPSC frequency was mimicked by a specific 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 1 microM), and the effects of tandospirone were prevented in the presence of a specific 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190, 1 microM). Activation of 5-HT1A receptors by 8-OH-DPAT (1 microM) evoked no direct postsynaptic effects in enzyme-treated isolated basolateral amygdala neurons, suggesting that tandospirone acts at presynaptic 5-HT1A receptors. Furthermore, this presynaptic inhibition by tandospirone was prevented after treatment with a pertussis toxin-sensitive GTP-binding protein (G-protein) inhibitor, N-ethylmaleimide (at 3 microM for 5 min). In conclusion, in the basolateral amygdala nuclei, tandospirone activated presynaptic 5-HT1A receptors on the GABAergic nerve terminals projecting to ovoid-shaped neurons and inhibited synaptic GABA transmission via G-proteins.
 ...
PMID:Presynaptic modulation of synaptic gamma-aminobutyric acid transmission by tandospirone in rat basolateral amygdala. 1106 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>