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Bladder distension and activation of the efferent function of sensory fibres: similarities with the effect of capsaicin.

1. The effects of the tachykinin NK2 receptor antagonist MEN 11420 (100 nmol kg(-1), i.v.) and isoprenaline (400 nmol kg(-1), i.v.) were compared in a model of distension-induced bladder activity in isovolumetric conditions. MEN 11420 induced a relaxation of the basal tone of the urinary bladder that was dependent on the volume of the viscus: the effect was absent at low volumes (0.2 and 0.5 ml) and it was maximal at high volumes of distension (1 and 2 ml), approaching about 60% of the isoprenaline-induced relaxation. The relaxant effect of isoprenaline was always evident at all volumes of distension. 2. Tetrodotoxin (1-100 microM, intravesically applied) abolished distension-evoked micturition contractions, but did not prevent the relaxant effect of MEN 11420- or isoprenaline on the bladder tone. 3. The cyclo-oxygenase inhibitor S-ketoprofen (0.5 micromol kg(-1), i.v.) produced a marked decrease of the bladder tone and a concomitant reduction of bladder motility at 1 ml volume of distension. At 2 ml of distension, S-ketoprofen still decreased the minimal pressure but had no significant effect on other parameters of vesical motility. In S-ketoprofen-pretreated rats, the relaxant effect of MEN 11420 was significant at 2 but not at 1 ml of distension, and that of isoprenaline was reduced by 50% at both 1 and 2 ml. 4. Ruthenium red (10 micromol kg(-1), i.v.) had no effect at a low volume of distension (0.2 ml) or at highest volume (2 ml) but decreased the basal tone and the frequency of bladder contractions at 1 ml of distension. In ruthenium red-pretreated rats, MEN 11420 failed to decrease bladder tone at 1 ml, whereas at 2 ml the effect of MEN 11420 was not different from that observed in controls (43 vs 60% of isoprenaline-induced relaxation, respectively). 5. At both 1 and 2 ml of distension, capsaicin pretreatment (164 micromol kg(-1), s.c. 5 days before) reduced the frequency of micturition contractions but had no effect on the bladder tone. Capsaicin pretreatment prevented the relaxant effect of MEN 11420 on the bladder tone both at 1 and at 2 ml of distension. 6. It is concluded that the release of tachykinins from capsaicin-sensitive afferent nerves induced by bladder distension is resistant to tetrodotoxin and to prostaglandin synthesis inhibition. Tachykinins modulate the vesical tone by acting through NK2 receptors.

Adrenergic beta-Agonists↗

Sex differences in chest pain in patients with documented coronary artery disease and exercise-induced ischemia: Results from the PIMI study.

BACKGROUND: Sex differences in the pathophysiologic course of coronary artery disease (CAD) are widely recognized, yet accurate diagnosis of coronary artery disease in women remains challenging. METHODS: To determine sex differences in the clinical manifestation of CAD, we studied chest pain reported during daily activities, exercise, and mental stress in 170 men and 26 women. All patients had documented CAD (>50% narrowing in at least 1 major coronary artery or prior myocardial infarction) and all had 1-mm ST-segment depression on treadmill exercise. We collected psychologic test results, serum samples (potassium, epinephrine, norepinephrine, cortisol, b-endorphin, and glucose), and cardiac function, sensory threshold, and autonomic function data at specified times before, during, or after exercise and mental stress tests to assess measures of depression, anxiety, and neurohormonal and thermal pain perception. RESULTS: Women reported chest pain more often than men during daily activities (P =.04) and during laboratory mental stressors (P =.01) but not during exercise. Men had lower scores than women on measures of depression, trait anxiety, harm avoidance, and reward dependence (P <.05 for all). Women had significantly lower plasma b-endorphin levels at rest (4.2 +/- 3.9 vs 5.0 +/- 2.5 pmol/L for men, P =.005) and at maximal mental stress (6.4 +/- 5.1 vs 7.4 +/- 3.5 pmol/L for men, P <.01). A higher proportion of women than men had marked pain sensitivity to graded heat stimuli applied to skin (hot pain threshold <41 degrees C, 33% vs 10%, P =.001). CONCLUSIONS: Our results reflect sex differences in the affective and discriminative aspects of pain perception and may help explain sex-related differences in clinical presentations.

Activities of Daily Living↗

Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal.

By means of extracellular recordings, individual norepinephrine-containing neurons in the locus coeruleus of unanesthetized behaviorally responsive rats and squirrel monkeys were found to respond to specific sensory and behavioral conditions. In rats, distinct clusters of action potentials followed the presentation of various nonnoxious auditory, visual, or somatosensory stimuli at latencies of 15-60 msec. Increased discharge rates were also seen during periods of spontaneous electroencephalogram arousal in both species. In monkeys, these cells responded most vigorously to complex arousing stimuli such as a preferred food. Because the noradrenergic innervation of most forebrain regions arises from the locus coeruleus, these results allow prediction of situations under which this massive projection system would be active and suggest a physiological role for this chemically identified network in specific behavioral processes.

Action Potentials↗

Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging.

We report that visual stimulation produces an easily detectable (5-20%) transient increase in the intensity of water proton magnetic resonance signals in human primary visual cortex in gradient echo images at 4-T magnetic-field strength. The observed changes predominantly occur in areas containing gray matter and can be used to produce high-spatial-resolution functional brain maps in humans. Reducing the image-acquisition echo time from 40 msec to 8 msec reduces the amplitude of the fractional signal change, suggesting that it is produced by a change in apparent transverse relaxation time T*2. The amplitude, sign, and echo-time dependence of these intrinsic signal changes are consistent with the idea that neural activation increases regional cerebral blood flow and concomitantly increases venous-blood oxygenation.

Brain Chemistry↗

Protonatable residues at the cytoplasmic end of transmembrane helix-2 in the signal transducer HtrI control photochemistry and function of sensory rhodopsin I.

Neutral residue replacements were made of 21 acidic and basic residues within the N-terminal half of the Halobacterium salinarium signal transducer HtrI [the halobacterial transducer for sensory rhodopsin I (SRI)] by site-specific mutagenesis. The replacements are all within the region of HtrI that we previously concluded from deletion analysis to contain sites of interaction with the phototaxis receptor SRI. Immunoblotting shows plasmid expression of the htrI-sopI operon containing the mutations produces SRI and mutant HtrI in cells at near wild-type levels. Six of the HtrI mutations perturb photochemical kinetics of SRI and one reverses the phototaxis response. Substitution with neutral amino acids of Asp-86, Glu-87, and Glu-108 accelerate, and of Arg-70, Arg-84, and Arg-99 retard, the SRI photocycle. Opposite effects on photocycle rate cancel in double mutants containing one replaced acidic and one replaced basic residue. Laser flash spectroscopy shows the kinetic perturbations are due to alteration of the rate of reprotonation of the retinylidene Schiff base. All of these mutations permit normal attractant and repellent signaling. On the other hand, the substitution of Glu-56 with the isosteric glutamine converts the normally attractant effect of orange light to a repellent signal in vivo at neutral pH (inverted signaling). Low pH corrects the inversion due to Glu-56 -> Gln and the apparent pK of the inversion is increased when arginine is substituted at position 56. The results indicate that the cytoplasmic end of transmembrane helix-2 and the initial part of the cytoplasmic domain contain interaction sites with SRI. To explain these and previous results, we propose a model in which (i) the HtrI region identified here forms part of an electrostatic bonding network that extends through the SRI protein and includes its photoactive site; (ii) alteration of this network by photoisomerization-induced Schiff base deprotonation and reprotonation shifts HtrI between attractant and repellent conformations; and (iii) HtrI mutations and extracellular pH alter the equilibrium ratios of these conformations.

Archaeal Proteins↗

The function of sensory information from the first somatosensory cortex for facial movements during ingestion in cats.

The aim of the present study was to investigate the relationship between the facial region of the first somatosensory cortex (facial SI) and facial region of the motor cortex (facial MI), as the basis of orofacial behaviors during ingestion of fish paste. Area M in the ventral cortex of the cruciate sulcus that was defined as part of the facial MI by and, showed various facial twitches evoked by intracortical microstimulation (ICMS) and recorded many mastication-related neurons (MRNs). Many MRNs in area M had receptive fields (RFs) in lingual, perioral and mandibular regions. The 60% value of activity patterns of MRNs (n = 124) recorded in area M of normal cats, were the pre-SB type (the sustained and pre-movement type) that showed increased firing prior to the start of mastication and then tonic activity during the masticatory period. MRNs recorded in area M of cats with the facial SI lesion, showed a noticeable decrease in MRNs with RFs in the perioral and mandibular regions and with activity of the pre-SB type. These results strongly suggest that blocking facial SI sensory inputs evoked by mastication interferes with the relay of important facial sensory information to area M required for the appropriate manipulation of food during mastication.

Acclimatization↗

Comparison of adult age differences in verbal and visuo-spatial memory: the importance of 'pure', parallel and validated measures.

The study compared age-related decrements in verbal and visuo-spatial memory across a broad elderly adult age range. Twenty-four young (18-25 years), 24 young-old (65-74 years), 24 middle-old (75-84 years) and 24 old-old (85-93 years) adults completed parallel recall and recognition measures of verbal and visuo-spatial memory from the Doors and People Test (Baddeley, Emslie & Nimmo-Smith, 1994). These constituted 'pure' and validated indices of either verbal or visuo-spatial memory. Verbal and visuo-spatial memory declined similarly with age, with a steeper decline in recall than recognition. Unlike recognition memory, recall performance also showed a heightened decline after the age of 85. Age-associated memory loss in both modalities was largely due to working memory and executive function. Processing speed and sensory functioning (vision, hearing) made minor contributions to memory performance and age differences in it. Together, these findings demonstrate common, rather than differential, age-related effects on verbal and visuo-spatial memory. They also emphasize the importance of using 'pure', parallel and validated measures of verbal and visuo-spatial memory in memory ageing research.

Adolescent↗

The mec-8 gene of Caenorhabditis elegans affects muscle and sensory neuron function and interacts with three other genes: unc-52, smu-1 and smu-2.

Mutations in the Caenorhabditis elegans gene mec-8 were previously shown to cause defects in mechanosensation and in the structure and dye filling of certain chemosensory neurons. Using noncomplementation screens, we have identified eight new mec-8 alleles and a deficiency that uncovers the locus. Strong mec-8 mutants exhibit an incompletely penetrant cold-sensitive embryonic and larval arrest, which we have correlated with defects in the attachment of body muscle to the hypodermis and cuticle. Mutations in mec-8 strongly enhance the mutant phenotype of unc-52(viable) mutations; double mutants exhibit an unconditional arrest and paralysis at the twofold stage of embryonic elongation, a phenotype characteristic of lethal alleles of unc-52, a gene previously shown to encode a homolog of the core protein of heparan sulfate proteoglycan, found in basement membrane, and to be involved in the anchorage of myofilament lattice to the muscle cell membrane. We have identified and characterized four extragenic recessive suppressors of a mec-8; unc-52(viable) synthetic lethality. The suppressors, which define the genes smu-1 and smu-2, can weakly suppress all mec-8 mutant phenes. They also suppress the muscular dystrophy conferred by an unc-52(viable) mutation.

Alleles↗

Oxytocin within auditory nuclei: a neuromodulatory function in sensory processing?

Oxytocin (OT) plays an important role in social bonding, ultrasonic vocalizations and other sexual behaviors in mammalian species. Although its presence within neuroendocrine regions in the forebrain is well established, its association with sensory nuclei remains unclear. We report here the presence of oxytocin immunoreactive neurons within several nuclei in the auditory brain stem of the mustached bat, Pteronotus parnellii. Immunocytochemical procedures revealed OT-immunoreactive perikarya and/or fiber terminals in restricted areas of the inferior colliculus (IC), superior olivary complex (SOC), including the medial and ventral nuclei of the trapezoid body, and in the cochlear nucleus. Perikarya were labeled predominantly in the IC and SOC and both perikarya and fiber terminals were labeled extensively in the cochlear nucleus.

Animals↗

Axotomy differentially regulates voltage-gated calcium currents in mice sensory neurones.

Medium sized dorsal root ganglion neurones are involved in tactile sensation and responsible for allodynia following nerve injury. We examined the effects of sciatic nerve injury on the expression of low and high voltage-gated calcium currents in medium sized neurones isolated from lumbar dorsal root ganglia of adult mice. Based on the relative expression of these calcium channel types, three populations of medium sized neurones were identified in controls. Type I, II and III populations were characterised respectively by small, predominant and no low voltage-gated current compared to the high voltage-gated current. Five days after nerve injury, calcium current expression was differentially affected by axotomy in these three subsets of medium neurones. Altogether, these results suggest that calcium channels are heterogeneously distributed among the medium sized neurones. This heterogeneity should provide specificity not only to sensory functions but also to sensory responses following nerve injury.

Animals↗

Nuptial gifts of male spiders function as sensory traps.

While nuptial food gifts come in various forms in arthropods, their evolutionary origins are unclear. A previous study on insects has shown that such gifts may arise as a sensory trap that exploits a female's underlying motivation to feed. Here I present independent evidence of a sensory trap in spiders. In certain visually oriented spiders, I suggest that males initially exploit the maternal care instinct by producing a nuptial gift that closely resembles the female egg sac. Males of the spider Pisaura mirabilis cover their prey gift with a silk layer, transforming it into a white round object. In a laboratory experiment I tested whether the colour of the gift affected the rate that females accepted males displaying their gifts. I found that the brighter and the more alike the nuptial gift to a female's egg sac, the faster the female responded by grabbing the gift. My results support the hypothesis that the nuptial gift in P. mirabilis works as a sensory trap.

Animals↗

Glutamate receptor functions in sensory relay in the thalamus.

It is known that glutamate is a major excitatory transmitter of sensory and cortical afferents to the thalamus. These actions are mediated via several distinct receptors with postsynaptic excitatory effects predominantly mediated by ionotropic receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate varieties (NMDA). However, there are also other kinds of glutamate receptor present in the thalamus, notably the metabotropic and kainate types, and these may have more complex or subtle roles in sensory transmission. This paper describes recent electrophysiological experiments done in vitro and in vivo which aim to determine how the metabotropic and kainate receptor types can influence transmission through the sensory thalamic relay. A particular focus will be how such mechanisms might operate under physiological conditions.

Afferent Pathways↗

Characterization and expression analysis of the murine rck gene: a protein kinase with a potential function in sensory cells.

We have characterized a murine protein kinase gene, rck, which was identified by crosshybridization with sequences from the v-ros tyrosine kinase gene under conditions of reduced stringency. cDNA analysis indicated that rck encodes a putative protein kinase related to the cdc2 subclass of the gene family and that the gene is identical to mak identified previously in the rat. An extensive expression analysis in the mouse performed by a combination of in situ hybridization and RNase protection revealed a novel and restricted pattern of expression: rck transcripts are found in two cell types involved in sensory transduction, photoreceptors and olfactory receptors as well as in epithelia of the respiratory tract and choroid plexus. Specific transcripts are also found in pre- and postmeiotic male germ cells. We suggest therefore that rck participates in signalling pathways important in a distinct set of cells, remarkably among them cells involved in sensory signal transduction.

Amino Acid Sequence↗

Effect of capsaicin on the rabbit urinary bladder. What is the function of sensory nerves that contain substance P?

The sensory innervation of the rabbit urinary bladder was studied using local application of the specific sensory neurotoxin capsaicin (8-methyl-N-vanillyl-6-nonenamide). This agent has its major effect by damaging small diameter unmyelinated sensory nerves. The drug produced a 51% reduction in the bladder content of the neuropeptide substance P. It therefore appears that a substantial proportion of the bladder's content of the peptide is to be found in capsaicin-sensitive sensory nerves. Cystometrograms carried out before and after treatment with capsaicin were similar; this suggests that capsaicin-sensitive sensory nerves may not be of importance in the afferent limb of the micturition reflex. In vitro muscle strip studies demonstrated a small reduction in the sensitivity of the detrusor muscle to electrical stimulation of its intramural nerves. It is possible that in vitro intramural nerve stimulation leads to release of neurotransmitters from sensory as well as motor nerves. It is proposed that small diameter sensory nerves in the bladder wall may have a role in the transmission of the sensation of pain and in the triggering of inflammatory reactions rather than forming the afferent limb of the micturition reflex.

Animals↗