Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “pathway analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,315 records · Page 73Linked to original sources
PubMed1999

Role of the feedforward command and reafferent information in the coordination of a passing prehension task.

The performances of a deafferented patient and five control subjects have been studied during a self-driven passing task in which one hand has to grasp an object transported by the other hand and in a unimanual reach-to-grasp task. The kinematics of the reach and grasp components and the scaling of the grip aperture recorded for the self-driven passing task were very similar in controls and the deafferented subject (GL). In contrast, for the unimanual task when vision was absent, GL's coordination between reaching and grasping was delayed in space and time compared with the control subjects. In addition, frequent reopening of the grip was observed in GL during the final closure phase of the unimanual prehension task. These results support the notion that afferent proprioceptive information resulting from the reaching movement - which seemed to be used to coordinate reaching and grasping commands in the unimanual task - is no longer necessary in the self-induced passing task. Finally, for the externally driven passing task, when the object was passively transported by the experimenter, the coordination was consistently modified in all subjects; grip aperture onset was delayed, thus asserting a specific contribution of the central command or feedforward mechanisms into the anticipation of the grasp onset observed in the self-driven passing task. The origin and nature of the information necessary for building up the feedforward mechanisms remains to be elucidated.

Adult↗
PubMed2001

Changes in the tonic activity of wrist extensor motor units induced by stimulating antagonistic group I afferents in humans.

The question as to whether the firing patterns of low- and high-threshold motor units in the extensor carpi radialis muscles are affected differently by group I afferents from the wrist flexors depending on the motor task being performed was investigated in six subjects. The motor units were voluntarily activated during a task consisting of either selectively contracting the wrist extensor muscles or co-activating the wrist and finger antagonist muscles by clenching the hand around a manipulandum. The motor units (n=40) were identified on the basis of their firing thresholds, their macro-potential areas, and their twitch contraction times. The effects on the motor-unit tonic activity of stimulating the wrist flexor afferents were assessed in terms of the changes in the firing probability, which were analysed after computing peri-stimulus time histograms using the cumulative sum procedure. Median nerve stimulation induced four main changes in the tonic firing pattern of the extensor motor units. An early, short-lasting increase in the firing probability (event E1) was found to occur in the high-threshold motor units, either in both tasks (6/13) or only during hand clenching (2/13). A short-latency decrease in the firing probability (event E2) was found to occur in all the motor units, the amount of which increased from the fast- to slowly contracting motor units, especially during hand clenching. A later decrease (event E3) followed by a large, late increase (event E4) in the tonic activity of the motor units was found to occur in all the motor units, without any task-dependent effects. All these various events were consistently observed in 12 pairs of motor units, each consisting of one slowly and one fast-contracting motor unit, which were tested simultaneously. These findings suggest that median nerve stimulation may selectively alter the tonic firing patterns of identified extensor motor units, depending on their functional characteristics (recruitment threshold, motor unit macro-potential area, contraction time) rather than on the excitatory drive to the motoneurone pool. The possible origins of these various events are discussed, and it is argued that, in the wrist extensor and flexor muscles that act as synergists during manipulatory finger movements and gripping tasks, the spinal pathways which assist the voluntary command may selectively modulate the firing patterns of identified motor units, to fit the requirements of the on-going motor task.

Action Potentials↗
PubMed2004

Mutational analysis of the hydantoin hydrolysis pathway in Pseudomonas putida RU-KM3S.

The biocatalytic conversion of 5-mono-substituted hydantoins to the corresponding D-amino acids or L-amino acids involves first the hydrolysis of hydantoin to a N-carbamoylamino acid by an hydantoinase or dihydropyrimidinase, followed by the conversion of the N-carbamoylamino acid to the amino acid by N-carbamylamino acid amidohydrolase ( N-carbamoylase). Pseudomonas putida strain RU-KM3S, with high levels of hydantoin-hydrolysing activity, has been shown to exhibit non-stereoselective hydantoinase and L-selective N-carbamoylase activity. This study focused on identifying the hydantoinase and N-carbamoylase-encoding genes in this strain, using transposon mutagenesis and selection for altered growth phenotypes on minimal medium with hydantoin as a nitrogen source. Insertional inactivation of two genes, dhp and bup, encoding a dihydropyrimidinase and beta-ureidopropionase, respectively, resulted in loss of hydantoinase and N-carbamoylase activity, indicating that these gene products were responsible for hydantoin hydrolysis in this strain. dhp and bup are linked to an open reading frame encoding a putative transport protein, which probably shares a promoter with bup. Two mutant strains were isolated with increased levels of dihydropyrimidinase but not beta-ureidopropionase activity. Transposon mutants in which key elements of the nitrogen regulatory pathway were inactivated were unable to utilize hydantoin or uracil as a nitrogen source. However, these mutations had no effect on either the dihydropyrimidinase or beta-ureidopropionase activity. Disruption of the gene encoding dihydrolipoamide succinyltransferase resulted in a significant reduction in the activity of both enzymes, suggesting a role for carbon catabolite repression in the regulation of hydantoin hydrolysis in P. putida RU-KM3S cells.

Acyltransferases↗
PubMed2003

Idiopathic spasmodic torticollis is not associated with abnormal kinesthetic perception from neck proprioceptive and vestibular afferences.

Proceeding from recent evidence for a sensory involvement in the pathophysiology of idiopathic spasmodic torticollis (ST), we asked whether the abnormal head posture of these patients is associated with distortions of their internal spatial reference frames due to abnormal processing of neck proprioceptive and/or vestibular input. Twelve ST patients were instructed to estimate, by adjusting a light pointer in the dark, their head and trunk mid-sagittal directions (as representatives of ego-centric references) and to reproduce a remembered target location in space (space centric reference). They did so before and after horizontal head and trunk rotations, which evoked isolated or combined vestibular and/or neck stimulation. In ST patients, unlike in normal controls, pre-stimulus estimates of the head and trunk mid-sagittal directions (baselines) showed a pronounced across-subjects variability, with essentially normal mean values. Their post-stimulus estimates in all tasks, after correction for the individual baseline errors, were normal with respect to both amplitude and variability, independent of stimulus direction, modality and rotation dynamics. Our findings suggest that ST patients have a rather inaccurate knowledge of their head posture, but can effectively use neck proprioceptive input and vestibular cues when estimating head and trunk displacements in ego-centric and space centric spatial orientation tasks. We propose that an offset of a non-sensory set point signal in the neck proprioceptive loop for head-on-trunk control may be responsible for the pathological head deviation in ST.

Adult↗
PubMed2005

Analysis of activated EGFR signalling pathways and their relation to laminin-5 gamma2 chain expression in oral squamous cell carcinoma (OSCC).

Overexpression of epidermal growth factor receptor (EGFR) was shown for the majority of squamous cell carcinomas. The EGFR expression correlates to tumour size, stage and cytoplasmic accumulation of the laminin-5 gamma2 chain (Ln-5/gamma2), which is known as a marker of invading tumour cells. There is only limited knowledge if and how EGFR signalling pathways are important for invasion-associated processes and for the regulation of Ln-5/gamma2. Therefore the distribution of phosphorylated Erk1/2, p38 MAPK and Akt was immunohistochemically defined in oral squamous cell carcinoma (OSCC) of different histological grade and compared to histological criteria of invasion and cytoplasmic Ln-5/gamma2 deposition. With raising histological grade, there is a slight increase in nuclear pErk1/2-stained tumour cells (P=0.398) and a loss of nuclear (P=0.593) and increased cytoplasmic staining (P=0.144) of pAkt mainly in invading OSCC cells. Nuclear pp38 MAPK could only be sporadically detected in few cases. In case of pErk1/2 and pAkt, only a partial co-localisation could be revealed in cases with abundant kinases and Ln-5/gamma2. Among the investigated kinases, only pAkt shows a relation to histological grade and invasion in OSCC. pErk1/2, pp38 MAPK and pAkt do not represent a direct link between EGFR and Ln-5 synthesis. Therefore, enhanced Ln-5/gamma2 may be a secondary phenomenon of EGFR-induced tumour cell proliferation and dissemination.

Biomarkers, Tumor↗
PubMed1998

Impact of temporal variation and the balance between excitation and inhibition on the output of the perfect integrate-and-fire model.

We consider how the output of the perfect integrate-and-fire (I&F) model of a single neuron is affected by the properties of the input, first of all by the distribution of afferent excitatory and inhibitory postsynaptic potential (EPSP, IPSP) inter-arrival times, discriminating particularly between short- and long-tailed forms, and by the degree of balance between excitation and inhibition (as measured by the ratio, r, between the numbers of inhibitory and excitatory inputs). We find that the coefficient of variation (CV; standard deviation divided by mean) of efferent interspike interval (ISI) is an increasing function of the length of the tail of the distribution of EPSP inter-arrival times and the ratio r. There is a range of values of r in which the CV of output ISIs is between 0.5 and 1. Too tight a balance between EPSPs and IPSPs will cause the model to produce a CV outside the interval considered to correspond to the physiological range. Going to the extreme, an exact balance between EPSPs and IPSPs as considered in [24] ensures a long-tailed ISI output distribution for which the moments such as mean and variance cannot be defined. In this case it is meaningless to consider quantities like output jitter, CV, etc. of the efferent ISIs. The longer the tail of the input inter-arrival time distribution, the less is the requirement for balance between EPSPs and IPSPs in order to evoke output spike trains with a CV between 0.5 and 1. For a given short-tailed input distribution, the range of values of r in which the CV of efferent ISIs is between 0.5 and 1 is almost completely inside the range in which output jitter (standard deviation of efferent ISI) is greater than input jitter. Only when the CV is smaller than 0.5 or the input distribution is a long-tailed one is output less than input jitter [21]. The I&F model tends to enlarge low input jitter and reduce high input jitter. We also provide a novel theoretical framework, based upon extreme value theory in statistics, for estimating output jitter, CV and mean firing time.

Action Potentials↗
PubMed2004

Altered expression of GFLO, the Gesneriaceae homologue of FLORICAULA/LEAFY, is associated with the transition to bulbil formation in Titanotrichum oldhamii.

Titanotrichum oldhamii inflorescences switch from flower to bulbil production at the end of the flowering season. The structure of the bulbiliferous shoots resembles the abnormal meristematic organization of the Antirrhinum mutant, floricaula. Gesneriaceae- FLORICAULA (GFLO) is thus a candidate gene in the regulation of bulbil formation. To investigate this hypothesis, part of the GFLO gene (between the second and third exon) was isolated using degenerate primers designed in regions conserved between Antirrhinum, Nicotiana and Arabidopsis, followed by genome walking to obtain the complete gene and flanking sequences. RT-PCR results showed that the GFLO homologue is strongly expressed in inflorescence apical meristems and young flowers. However, in meristems that had switched to bulbil formation, GFLO transcription was greatly reduced. The down-regulation of GFLO in bulbil primordia indicates that this gene is connected to, or part of, the bulbil-flower regulatory pathway. Phylogenetic analysis confirms the orthology of GFLO and FLO, and indicates that the gene may be useful for phylogenetic reconstruction at the genus or family level.

Amino Acid Sequence↗
PubMed2004

Reverse genetic analysis of the glutathione metabolic pathway suggests a novel role of PHGPX and URE2 genes in aluminum resistance in Saccharomyces cerevisiae.

We have taken a systematic genetic approach to study the potential role of glutathione metabolism in aluminum (Al) toxicity and resistance, using disruption mutants available in Saccharomyces cerevisiae. Yeast disruption mutants defective in phospholipid hydroperoxide glutathione peroxidases (PHGPX; phgpx1 Delta, phgpx2 Delta, and phgpx3Delta), were tested for their sensitivity to Al. The triple mutant, phgpx1 Delta/2Delta/3Delta, was more sensitive to Al (55% reduction in growth at 300 microM Al) than any single phgpx mutant, indicating that the PHGPX genes may collectively contribute to Al resistance. The hypersensitivity of phgpx3Delta to Al was overcome by complementation with PHGPX3, and all PHGPX genes showed increased expression in response to Al in the wild-type strain (YPH250), with maximum induction of approximately 2.5-fold for PHGPX3. Both phgpx3Delta and phgpx1Delta/2Delta/3Delta mutants were sensitive to oxidative stress (exposure to H(2)O(2) or diamide). Lipid peroxidation was also increased in the phgpx1Delta/2Delta/3Delta mutant compared to the parental strain. Disruption mutants defective in genes for glutathione S-transferases (GSTs) (gtt1Delta and gtt2Delta), glutathione biosynthesis (gsh1Delta and gsh2Delta), glutathione reductase (glr1Delta) and a glutathione transporter (opt1Delta) did not show hypersensitivity to Al relative to the parental strain BY4741. Interestingly, a strain deleted for URE2, a gene which encodes a prion precursor with homology to GSTs, also showed hypersensitivity to Al. The hypersensitivity of the ure2Delta mutant could be overcome by complementation with URE2. Expression of URE2 in the parental strain increased approximately 2-fold in response to exposure to 100 microM Al. Intracellular oxidation levels in the ure2Delta mutant showed a 2-fold (non-stressed) and 3-fold (when exposed-to 2 mM H(2)O(2)) increase compared to BY4741; however, the ure2Delta mutant showed no change in lipid peroxidation compared to the control. The phgpx1Delta/2Delta/3Delta and ure2Delta mutants both showed increased accumulation of Al. These findings suggest the involvement of PHGPX genes and a novel role of URE2 in Al toxicity/resistance in S. cerevisiae.

Aluminum↗
PubMed1997

Genetic evidence for 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) as a negative effector of cytochrome terminal oxidase cbb3 production in Rhizobium etli.

A Rhizobium etli Tn5mob-induced mutant (CFN035) exhibits an enhanced capacity to oxidize N,N,N',N', tetramethyl-p -phenylenediamine (TMPD), a presumptive indicator of elevated cytochrome c terminal oxidase activity. Sequencing of the mutated gene in CFN035 revealed that it codes for the amidophosphoribosyl transferase enzyme (PurF) that catalyzes the first step in the purine biosynthetic pathway. Two c-type cytochromes with molecular weights of 32 and 27 kDa were produced in strain CFN035, which also produced a novel CO-reactive cytochrome (absorbance trough at 553 nm), in contrast to strain CE3 which produced a single 32 kDa c-type protein and did not produce the 553 nm CO-reactive cytochrome. A wild-type R. etli strain that expresses the Bradyrhizobium japonicum fixNOQP genes, which code for the symbiotic cytochrome terminal oxidase cbb3, produced similar absorbance spectra (a trough at 553 nm in CO-difference spectra) and two c-type proteins similar in size to those of strain CFN035, suggesting that CFN035 also produces the cbb3 terminal oxidase. The expression of a R. etli fixN-lacZ gene fusion was measured in several R. etli mutants affected in different steps of the purine biosynthetic pathway. Our analysis showed that purF, purD, purQ, purL, purY, purK and purE mutants expressed three-fold higher levels of the fixNOQP operon than the wild-type strain. The derepressed expression of fixN was not observed in a purH mutant. The purH gene product catalyzes the conversion of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to 5-form-aminoimidazole-4-carboxamide ribonucleotide (FAICAR) and inosine. Supplementation with AICA riboside lowered the levels of fixN expression in the purF mutants. These data are consistent with the possibility that AICAR, or a closely related metabolite, is a negative effector of the production of the symbiotic terminal oxidase cbb3 in R. etli.

Amidophosphoribosyltransferase↗
PubMed1997

Characterization of Streptomyces nogalater genes encoding enzymes involved in glycosylation steps in nogalamycin biosynthesis.

The sno gene cluster in Streptomyces nogalater ATCC 27451 contains the nogalamycin biosynthesis genes. A set of plasmid constructions carrying fragments of the sno cluster that lie downstream of snoD were used to complement the S. galilaeus mutant H039, which is blocked in rhodosamine and 2-deoxyfucose biosynthesis in the aclacinomycin pathway. Sequence analysis of this cluster revealed three contiguous open reading frames (ORFs) that were designated snoF, snoG, and snoH. Only those plasmid constructs that expressed SnoG were able to complement H039. SnoG shows similarity to GalE, a UDP-glucose-4-epimerase catalyzing the epimerization of UDP-glucose to UDP-galactose. The putative SnoF protein is similar to 3,5-epimerases involved in rhamnose biosynthesis. The deduced product of snoH is a 489-amino acid polypeptide. It is similar to the product of dau ORF3 found in the daunomycin cluster. However its function is still unclear. Based on the complementation experiments and sequence analysis, this part of the sno cluster is suggested to be involved in the biosynthesis of the sugar portion of nogalamycin. Interestingly, SnoA, a transcriptional activator for the sno minimal polyketide synthase, is also needed to express this cluster.

Aclarubicin↗
PubMed2004

Incorporation of 1-chlorooctadecane into FA and beta-hydroxy acids of Marinobacter hydrocarbonoclasticus.

The lipids of the gram-negative marine bacterium Marinobacter hydrocarbonoclasticus, cultivated in synthetic seawater supplemented with 1-chlorooctadecane as sole source of carbon, were isolated, purified, and their structures determined. Three pools of lipids were isolated according to the sequential procedure used: unbound lipids extracted by organic solvents, ester-bound lipids released under alkaline conditions, and amide-bound lipids released by acid hydrolysis. FA isolated from the unbound lipids included omega-chlorinated (21%, w/w, of this fraction; C16 predominant) and nonchlorinated compounds (22%, w/w; C18 predominant). These acids were accompanied by a high proportion of omega-chloro-C18 alcohols (43%, w/w) and a lower amount of omega-chloro-beta-hydroxy-C18, -C16, and -C14 acids (5%, w/w). These data, together with the isolation from the culture medium of gamma-butyrolactone, suggested a metabolism of 1-chlorooctadecane through oxidation into omega-chloro acid and then the classic beta-oxidation pathway. The analysis of the ester-bound and amide-bound lipids revealed that significant amounts of omega-chloro-beta-hydroxy C10-C12 acids were incorporated into the lipopolysaccharides of the bacterium. Incorporation of these omega-chloro-beta-hydroxy acids into the lipopolysaccharides represents a novel route for chloroalkane assimilation in hydrocarbonoclastic gram-negative bacteria. The formation of chlorinated hydroxy acids, like the omega-chloro FA in the cellular lipids, could account for an incomplete mineralization of chloroparaffins in the environment.

Fatty Acids↗
PubMed1981

The action of norepinephrine in the rat hippocampus: intracellular studies in the slice preparation.

The ionic basis of norepinephrine (NE) action was studied with intracellular recording techniques in the rat hippocampal slice. Topical application of NE caused, in CA1 neurons, a 3-4 mV hyperpolarization associated with a 10-20% decrease in input resistance. This effect was accompanied by a decrease in spontaneous action potential discharges and, in some cells, by a reduction in EPSPs produced by stimulation of the excitatory Schaffer collateral-commissural pathway. An analysis of the voltage and concentration dependency revealed that NE may activate two different mechanisms. Experiments performed to test this hypothesis have demonstrated that a short duration hyperpolarizing action of NE was still present in a low Cl- medium. The hyperpolarizing responses to NE were absent in ouabain-treated slices and in low temperature. Cyclic AMP produced a 3-4 mV hyperpolarization associated with minimal changes in input resistance. This effect of cAMP was blocked by ouabain. IBMX potentiated responses to low concentrations of NE. It is proposed that NE activates two mechanisms; one involves activation of Cl- conductance and the other activation of a Na+-K+ pump. This latter effect might be mediated by cAMP.

Animals↗
PubMed1982

Brain-specific ceramide synthesis activity: change during brain maturation and in jimpy mouse brain.

The synthesis of ceramide from lignoceric acid was studied in normally developing rat brain and jimpy mouse brain. The developmental pattern of the synthesis of both non-hydroxy and hydroxyceramide from free lignoceric acid in a brain-specific pathway requiring NADPH and cytosolic factors was similar to the synthesis from lignoceroyl CoA and both showed increasing activity during myelination. There were no differences in non-hydroxyceramide synthesis between jimpy and normal littermate control mouse brains by both pathways. HPLC analysis showed the same non-hydroxyceramide level in both types of brains.

Aging↗
PubMed1984

A [14C]2-deoxyglucose analysis of the functional neural pathways of the limbic forebrain in the rat. IV. A pathway from the prefrontal cortical-medial thalamic system to the hypothalamus.

The present study utilized the [14C]2-deoxyglucose (2-DG) cell labeling procedure to characterize a functional pathway from the prefrontal cortex (Pfc) and mediodorsal thalamic nucleus (MD) to the hypothalamus. Rats were injected with 2-DG prior to a 45 min experimental paradigm consisting of alternating 30 s on-off periods of electrical brain stimulation. Standard procedures were utilized for the removal and processing of brain tissue for X-ray autoradiography. In the first phase of this study, stimulation applied to the prefrontal cortex generally yielded a pattern of 2-DG distribution consistent with the findings of classical anatomical studies. Stimulation of the dorsomedial and ventromedial prefrontal cortex or the infralimbic cortex produced the most effective activation of the diencephalon. This activation was primarily limited to MD, with no involvement of any region of the hypothalamus. In the second phase of this study, brain regions activated following stimulation of sites along the rostro-caudal axis of MD were examined. Stimulation of MD resulted in the activation of the nucleus reuniens and other midline and non-specific thalamic nuclei. Stimulation of this nucleus also activated the ventromedial thalamic nucleus, medial aspects of the nucleus accumbens and the medial and sulcal prefrontal cortices. Again, in each of these cases, labeling within any region of the hypothalamus could not be detected. Since MD stimulation activated the midline thalamus, and the nucleus reuniens in particular, the last phase of this experiment involved stimulation of the nucleus reuniens in order to determine the source of medial thalamic inputs to the hypothalamus. Stimulation of the nucleus reuniens activated fibers which were distributed to both the medial and lateral hypothalamus. In addition, stimulation also activated the descending periventricular system, which could be followed to the level of the midbrain central gray and such limbic structures as the hippocampal formation, septal area, amygdala and prefrontal cortex. These findings indicate that Pfc-MD activation of the hypothalamus is achieved indirectly via interneurons within the nucleus reuniens.

Animals↗
PubMed1985

A [14C]2-deoxyglucose analysis of the functional neural pathways of the limbic forebrain in the rat. V. The septal area.

The [14C]2-deoxyglucose (2-DG) metabolic mapping technique has been used to identify the regions responding with an augmented rate of metabolism following focal electrical stimulation of various sites within the lateral septal nucleus and medial septal nucleus/diagonal band (MSN/DB) complex in the rat. Since 2-DG uptake has been correlated with rates of functional activity, it was the intention of this study to suggest the anatomical substrates underlying various physiological and behavioral responses elicited by stimulation of the septal area. The results show that stimulation of any region within the lateral septal nucleus produced a profound bilateral activation of both the lateral septal nucleus, as well as the hippocampal formation. While stimulation of a number of different fiber systems associated with the lateral septum could contribute to the observed pattern of labeling, the data suggest that, functionally, a major consequence of such stimulation is the antidromic activation of CA3----lateral septum fibers to axonal branch points, beyond which, orthodromic propagation of the impulse produces activation in CA3 target regions, including subfields CA1 and CA3, as well as the lateral septal nucleus, bilaterally. In addition, regions typically manifesting metabolic activation following stimulation of the lateral septal nucleus included the ipsilateral diagonal band of Broca, nucleus accumbens, lateral preoptic area and lateral hypothalamus, posteriorly, and the prelimbic cortex, anteriorly. Occasionally, target regions of the postcommissural fornix, including the medial mammillary nucleus and anterior thalamic nuclei were also activated following stimulation of the lateral septal nucleus. In contrast to the widespread pattern of activation resulting from stimulation of the lateral septal nucleus, stimulation of the MSN/DB complex produced activation which was largely confined to the medial forebrain bundle. In a final phase of the experiment, afterdischarge activity was elicited by sodium penicillin injection into the lateral septal nucleus. Such treatment produced more widespread 2-DG uptake, including more extensive activation within the lateral septal nucleus, hippocampal formation, amygdala, and thalamus. Additionally, the prefrontal cortex and temporal neocortex were activated.

Animals↗
PubMed1990

Vagal afferent-mediated inhibition of a nociceptive reflex by intravenous serotonin in the rat. I. Characterization.

The effect of intravenous (i.v.) serotonin (5-HT) on nociception and blood pressure was examined in male Sprague-Dawley rats. Intravenous 5-HT produced a dose-dependent (6-192 micrograms/kg, i.v.) inhibition of the nociceptive tail-flick (TF) reflex in lightly pentobarbital-anesthetized (ED50 = 40 micrograms/kg) and conscious rats (ED50 = 44 micrograms/kg). In the lightly pentobarbital-anesthetized rat, the blood pressure response to i.v. 5-HT was typically a triphasic response with a marked Bezold-Jarisch reflex-induced decrease in pressure (associated with a brief period of apnea) followed by a pressor phase and a subsequent delayed hypotension. In the conscious rat, the response was typically biphasic with the late hypotensive phase absent. A variety of anatomical and pharmacological manipulations were performed to characterize the 5-HT-induced inhibition of the TF reflex and associated changes in blood pressure. Prevention of 5-HT-induced reflex apnea by artificial ventilation did not affect inhibition of the TF reflex produced by 5-HT. Pharmacological manipulations were performed to mimic, as closely as possible, the acute increases and decreases in blood pressure associated with i.v. 5-HT. Nitroprusside (8 micrograms/kg, i.v.) produced a decrease in blood pressure of similar magnitude and rate as that associated with the Bezold-Jarisch reflex-induced decrease in pressure produced by 72 micrograms/kg 5-HT, but did not change TF latency from baseline. Similarly, acute increases in pressure produced by phenylephrine (8 micrograms/kg, i.v.), intended to mimic the secondary pressor effect of 5-HT, did not change TF latency. The short-acting ganglion blocker trimethaphan (5 mg/kg, i.v.) closely mimicked the late hypotensive phase produced by 5-HT, but again resulted in no change in TF latency. Pretreatment with the ganglion blocker chlorisondamine (2.5 mg/kg) abolished all depressor responses to 72 micrograms/kg 5-HT, but did not significantly affect the TF reflex. These results indicate that acute changes in blood pressure and respiration associated with i.v. 5-HT do not contribute to inhibition of the TF reflex. This conclusion was confirmed in experiments in which bilateral vagotomy abolished approximately 70% of the 5-HT-induced inhibition of the TF reflex (and all depressor responses), and resulted in a significantly greater pressor response. Finally, low thoracic spinal cord transection (T9-10) abolished the inhibition of the TF reflex produced by i.v. 5-HT. Therefore, 5-HT stimulates vagal afferents and inhibits the TF reflex by activating descending inhibitory systems from the brainstem.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1991

Unmyelinated primary afferent fiber stimulation depletes dynorphin A (1-8) immunoreactivity in rat ventral horn.

The present study demonstrates many dynorphin (DYN)-immunoreactive fibers and presumed presynaptic terminals in rat lumbar ventral horn. The fibers and terminals seem to arise largely from DYN-containing intrinsic neurons in the dorsal horn. The majority of the presumed terminals closely surround a subpopulation of motoneurons that tend to be located in flexor motoneuron columns. Acute C fiber, but not A fiber, primary afferent stimulation depletes the ventral horn DYN immunostaining. We interpret these findings to indicate that the spinal DYN neurons are well positioned to serve both as modulators of nociceptive input and as interneurons in motor reflexes. We further hypothesize that the depletion of DYN-immunoreactivity that follows either acute C fiber stimulation or intense nociceptive stimuli may be the trigger for the upregulation in spinal cord DYN that occurs in models of chronic pain states.

Afferent Pathways↗
PubMed1993

Alpha 1-adrenoceptors in the adult rat barrel field: effects of deafferentation and norepinephrine removal.

Norepinephrine (NE), acting on brain adrenoceptors, plays an important role in barrel field neuronal activity and plasticity. For this reason, the distribution of alpha 1- and alpha 2-adrenoceptors in the somatosensory cortex barrel field was studied by autoradiographic techniques in rats undergoing plastic change or NE depletion. In layers IV and V of the cortex, the pattern of alpha 1-adrenoceptors (assessed by [3H]prazosin binding) varied across the barrel field. There was relatively low binding within the barrels themselves, with 21% higher binding in the surrounding septa. alpha 2-Adrenoceptor binding (assessed with [3H]paraminoclonidine) was almost homogeneous across the entire barrel field. Two weeks after noradrenergic deafferentation by unilateral lesioning of the locus coeruleus, there was a 16% upregulation of [3H]prazosin binding. This then returned to control levels of by 8 weeks. Peripheral deafferentation of sensory input to the barrel field produced the opposite effect on alpha 1-adrenoceptors. Unilateral removal of all but the central (C3) vibrissa (which induces plastic changes in the cortical representation of the spared virbrissa) caused a 12% decrease in [3H]prazosin binding in the whole barrel field at 2 weeks after surgery which returned to normal by 8 weeks. Therefore, alpha 1-adrenoceptors in the barrel field of the rat are affected in opposite ways by changes in NE content and afferent sensory input. We hypothesize that alpha 1-adrenoceptor levels are modulated after vibrissectomy through either an indirect reaction to reduced cortical gamma-aminobutyric acid levels, or by a reordering of metabolic priorities during plastic change of the cortical neuronal network.

Afferent Pathways↗