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PubMed2000

Additive satiety-delaying effects of capsaicin-induced visceral deafferentation and NMDA receptor blockade suggest separate pathways.

Both ablation of visceral afferents and blockade of NMDA receptor-mediated glutamatergic transmission by MK-801 result in overconsumption of sucrose solution and other food, apparently by interrupting visceral signals and thus delaying satiation. If these two manipulations act on the same pathway, namely, the propagation of vagal afferent signals to NTS neurons, their effects would be expected to be non-additive. To test this hypothesis, two groups of rats - one with prior systemic capsaicin (n=11) and one with vehicle treatment (n=10) - were trained to drink 15% sucrose solution after 15 h food deprivation every 3-4 days, and then injected with MK-801 (100 microg/kg, i.p.) or saline. Both capsaicin and MK-801 produced the expected significant (P<.001) increase in 30 and 60 min sucrose intake if compared to their respective controls. Administration of MK-801 to capsaicin-treated rats further increased 60 min sucrose intake significantly (P<.001) in a fully additive fashion. These results suggest that the two treatments do not impinge on the same neural pathway to delay satiation. MK-801 may interfere with signals from capsaicin-resistant vagal afferents, or alternatively may act on other areas in the brain or periphery.

Animals↗

PubMed2004

Restraint stress delays solid gastric emptying via a central CRF and peripheral sympathetic neuron in rats.

Central corticotropin-releasing factor (CRF) delays gastric emptying through the autonomic nervous system. CRF plays an important role in mediating delayed gastric emptying induced by stress. However, it is not clear whether a sympathetic or parasympathetic pathway is involved in the mechanism of central CRF-induced inhibition of solid gastric emptying. The purpose of this study was to investigate whether 1) CRF inhibits solid gastric emptying via a peripheral sympathetic pathway and 2) stress-induced inhibition of solid gastric emptying is mediated via a central CRF and peripheral sympathetic pathways. Using male Sprague-Dawley rats, CRF was injected intracisternally with or without various adrenergic-blocking agents. To investigate whether central CRF-induced inhibition of solid gastric emptying is mediated via a peripheral sympathetic pathway, rats underwent celiac ganglionectomy 1 wk before the gastric emptying study. After solid meal ingestion (90 min), gastric emptying was calculated. To investigate the role of endogenous CRF in stress-induced delayed gastric emptying, a CRF type2 receptor antagonist, astressin2-B, was intracisternally administered. Rats were subjected to a restraint stress immediately after the feeding. Intracisternal injection of CRF (0.1-1.0 microg) dose-dependently inhibited solid gastric emptying. The inhibitory effect of CRF on solid gastric emptying was significantly blocked by guanethidine, propranolol, and celiac ganglionectomy but not by phentolamine. Restraint stress significantly delayed solid gastric emptying, which was improved by astressin2-B, guanethidine, and celiac ganglionectomy. Our research suggests that restraint stress inhibits solid gastric emptying via a central CRF type2 receptor and peripheral sympathetic neural pathway in rats.

Animals↗

PubMed1981

Some effects of auditory stimulation on perioral motor unit discharge and their implications for speech production.

The objective of this investigation was to describe the electrophysiological properties of short-latency reflexive pathways existing between the auditory system and the motoneurons involved in the control of lower lip movements for speech. The general procedure involved binaural presentation of auditory clicks (60--75 dB SL) at constant rates while subjects maintained a steady firing rate in a perioral motor unit. Post-stimulus time histograms were used to assess the effects of stimulation on the probability of firing of individual motor units. Data collected on 33 motor units in four subjects revealed a significant short-latency change in the probability of firing of 16 of these units. The mean latency of this effect was 20.4 ms. There was some indication that the direction and latency of the initial response to stimulation was dependent on the location and function of individual motor units. The likely neural pathways mediating these effects and their potential role in speech production are discussed.

Acoustic Stimulation↗

PubMed1998

A neurological dissociation between preserved visual and impaired spatial processing in mental imagery.

Studies on primates have shown that visual and spatial perceptual analysis depends on two separate neural pathways, associated with the processing of "what" and "where" an object is (visual characteristics and spatial coordinates, respectively). Similar dichotomies have been proposed by cognitive psychologists (e.g., the contrast between visual and spatial processing in working memory) and by neuropsychologists (e.g., the distinction between topographic agnosia and amnesia). In this paper we report the case of a patient with a severe spatial disorientation whose perceptual processing of visual and spatial information was normal, but in imagery tasks she had a dissociation between preserved visual and impaired spatial processing. While her ability to represent objects visually was intact, she failed in any task requiring mental rotation, recall of spatial position or execution of spatially based imagery operations. The case clearly demonstrates that visual and spatial imagery are functionally independent processes which must rely on different underlying neural systems. This pattern of impairment also explains the associated topographical amnesia as an inability to integrate spatial information in a mental map.

Aged↗

PubMed1998

Modification of auditory pathway functions in patients with hearing improvement after middle ear surgery.

We recorded auditory-evoked magnetic responses with a whole-scalp 122-channel neuromagnetometer from seven adult patients with unilateral conductive hearing loss before and after middle ear surgery. The stimuli were 50-msec 1-kHz tone bursts, delivered to the healthy, nonoperated ear at interstimulus intervals of 1, 2, and 4 seconds. The mean preoperative pure-tone average in the affected ear was 57 dB hearing level; the mean postoperative pure-tone average was 17 dB. The 100-msec auditory-evoked response originating in the auditory cortex peaked, on average, 7 msecs earlier after than before surgery over the hemisphere contralateral to the stimulated ear and 2 msecs earlier over the ipsilateral hemisphere. The contralateral response strengths increased by 5% after surgery; ipsilateral strengths increased by 11%. The variation of the response latency and amplitude in the patients who underwent surgery was similar to that of seven control subjects. The postoperative source locations did not differ noticeably from preoperative ones. These findings suggest that temporary unilateral conductive hearing loss in adult patients modifies the function of the auditory neural pathway.

Adaptation, Physiological↗

PubMed2004

Targeted sensory restoration to the upper aerodigestive tract with physiologic implications.

BACKGROUND: Sensory restoration through sensate flaps placed into critical areas of the upper aerodigestive tract is an attractive reconstructive goal to achieve optimal post-therapy function. The question that has remained unanswered is whether sensory recovery takes place through the newly established neural pathway or through ingrowth of sensory nerves from the periphery of the defect. METHODS: Three patients with squamous cell cancer underwent resection and primary reconstruction of the laryngopharynx with a sensate radial forearm flap. The flaps were designed with a smaller, proximal paddle to serve as a monitor. Reneurotization of the flaps was carried out to the superior laryngeal nerve. RESULTS: All three patients were followed for a minimum of 12 months. Each of these patients reported the development of a cough that resulted from stimulation of the external monitor. This phenomenon was easily duplicated by light stimulation of the monitor, which not only produced the cough but was consistently perceived by the patient as arising from inside their throat. CONCLUSIONS: This series conclusively demonstrates that sensory feedback can be restored in a targeted fashion through neural anastomoses and that a physiologic response that helps in airway protection can be produced through the use of sensate flaps with a strategically selected recipient nerve.

Anastomosis, Surgical↗

PubMed2004

Energy balance and reproduction.

The physiological mechanisms that control energy balance are reciprocally linked to those that control reproduction, and together, these mechanisms optimize reproductive success under fluctuating metabolic conditions. Thus, it is difficult to understand the physiology of energy balance without understanding its link to reproductive success. The metabolic sensory stimuli, hormonal mediators and modulators, and central neuropeptides that control reproduction also influence energy balance. In general, those that increase ingestive behavior inhibit reproductive processes, with a few exceptions. Reproductive processes, including the hypothalamic-pituitary-gonadal (HPG) system and the mechanisms that control sex behavior are most proximally sensitive to the availability of oxidizable metabolic fuels. The role of hormones, such as insulin and leptin, are not understood, but there are two possible ways they might control food intake and reproduction. They either mediate the effects of energy metabolism on reproduction or they modulate the availability of metabolic fuels in the brain or periphery. This review examines the neural pathways from fuel detectors to the central effector system emphasizing the following points: first, metabolic stimuli can directly influence the effector systems independently from the hormones that bind to these central effector systems. For example, in some cases, excess energy storage in adipose tissue causes deficits in the pool of oxidizable fuels available for the reproductive system. Thus, in such cases, reproduction is inhibited despite a high body fat content and high plasma concentrations of hormones that are thought to stimulate reproductive processes. The deficit in fuels creates a primary sensory stimulus that is inhibitory to the reproductive system, despite high concentrations of hormones, such as insulin and leptin. Second, hormones might influence the central effector systems [including gonadotropin-releasing hormone (GnRH) secretion and sex behavior] indirectly by modulating the metabolic stimulus. Third, the critical neural circuitry involves extrahypothalamic sites, such as the caudal brain stem, and projections from the brain stem to the forebrain. Catecholamines, neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) are probably involved. Fourth, the metabolic stimuli and chemical messengers affect the motivation to engage in ingestive and sex behaviors instead of, or in addition to, affecting the ability to perform these behaviors. Finally, it is important to study these metabolic events and chemical messengers in a wider variety of species under natural or seminatural circumstances.

Animals↗

PubMed2003

Allografted fetal dorsal root ganglion neuronal survival in the guinea pig cochlea.

Neural grafting is a potential strategy to help restore auditory function following loss of spiral ganglion cells. As a first step towards the reconstruction of a neural pathway from the cochlea to the brainstem, we have examined the survival of fetal dorsal root ganglion (DRG) neurons allografted into the cochlea of adult guinea pigs. In some animals implantation of DRGs was combined with a local infusion of neurotrophic substances whereas in others auditory sensory receptors were chemically destroyed prior to DRG implantation by injection of the ototoxin neomycin into the middle ear. The results show that many transplanted DRG neurons attached close to the cochlear spiral ganglion neurons. The survival of the implant was significantly increased by treatment with neurotrophic factors, but not reduced by the absence of auditory sensory structures. This study shows that implanted sensory neurons can survive heterotopic grafting immediately adjacent to the eighth cranial nerve, thereby providing a basis for further studies of the anatomical and functional influence of neural grafts in the inner ear.

Animals↗

PubMed1999

Systemic administration of lipopolysaccharide induces release of nitric oxide and glutamate and c-fos expression in the nucleus tractus solitarii of rats.

There is increasing recognition that communication pathways exist between the immune system and brain, which allows bidirectional regulation of immune and brain responses to infection. The endotoxin lipopolysaccharide (LPS) has been reported to elicit release of cytokines and expression of inducible nitric oxide synthase (iNOS) in peripheral organs. Whereas LPS given systemically causes endotoxic shock, little is known about its central nervous system action, particularly the induction of iNOS. Nitric oxide (NO) and glutamate in the nucleus tractus solitarii (NTS) are important mediators of central cardiovascular regulation. We have previously demonstrated that intravenous injections of LPS increased the NO precursor L-arginine-induced depressor effect in the NTS. The present study investigated further the effects of LPS on the release of NO and glutamate in the NTS and the expression of c-fos, an immediate early response gene product, in neural substrates for central cardiovascular control. In vivo microdialysis coupled with chemiluminescence and electrochemical detection techniques were used to measure extracellular levels of NO and glutamate in the rat NTS. Immunohistochemistry was used for the examination of c-fos protein expression. We found that intravenous infusion of LPS (10 mg/kg) produced a biphasic depressor effect, with an early, sharp hypotension that partially recovered in 15 minutes and a secondary, more prolonged hypotension. In the NTS, a progressive increase of extracellular glutamate and NO levels occurred 3 and 4 hours after LPS was given, respectively. The effects of LPS on the induction of delayed hypotension and NO formation in the NTS were abolished by pretreatment with the iNOS inhibitor aminoguanidine. Finally, c-fos protein expression in the NTS and related structures for cardiovascular regulation was observed after LPS challenge. Taken together, these data suggest that an endotoxin given systemically can elicit delayed increases of glutamate release and iNOS-dependent NO production in the NTS and activate the central neural pathway for modulating cardiovascular function.

Animals↗

PubMed1995

Mechanism of neuroinvasion of Venezuelan equine encephalitis virus in the mouse.

Venezuelan equine encephalitis virus (VEE) causes a biphasic disease in mice following subcutaneous inoculation in the footpad. In the initial phase, virus replicates primarily in the lymphoid tissues and induces a high titer viremia. Subsequently, the virus invades the central nervous system (CNS) from the circulation, and an encephalitis ensues. At the earliest times that VEE specific in situ hybridization signal was observed in the CNS, it was in areas of the brain involved in olfaction, leading to the hypothesis that virus may invade the brain from the circulation through the olfactory system. The results presented in this paper define the route of CNS invasion in experimental murine VEE disease initiated by subcutaneous inoculation. Virus circulating in the blood appears to seed specific areas of the peripheral nervous system during the viremic lymphoid phase of the illness. Virus replication within olfactory and dental tissues is followed by centripetal spread of virus along neural pathways. Virus enters the brain in a pattern reflecting the proximity of the peripheral invasion site to the CNS. Specifically, virus is first found in the brain within the structures of the olfactory system, followed by areas innervated by the trigeminal nerve. Virus later disseminates along fiber tracts and connected circuits within the brain, resulting in a disseminated meningoencephalitis. Surgical or chemical interruption of the olfactory system at the level of the olfactory neuroepithelium or the main olfactory bulb inhibited entry of VEE into the CNS through the olfactory nerve. However, the olfactory route is not absolutely required for CNS invasion, as virus invaded the CNS of olfactory ablated animals through the trigeminal nerve. These observations are consistent with a model of hematogenous seeding of the peripheral nervous system, followed by invasion of the CNS by direct neural spread.

Animals↗

PubMed1983

Thalamic nucleus ventro-postero-lateralis inhibits nucleus parafascicularis response to noxious stimuli through a non-opioid pathway.

These experiments investigated the role of a specific thalamic nucleus in the cellular response to noxious and non-noxious inputs. Single-unit extracellular responses to peripheral noxious stimuli were recorded with glass micropipettes in the nucleus parafascicularis (Pf) of the rat under chloral hydrate anesthesia. Bipolar stimulating/recording electrodes were inserted in the nucleus ventro-postero-lateralis (VPL) of the thalamus, in areas responsive to the peripheral noxious stimulation. Single-unit records in Pf and multi-unit records in VPL demonstrated that both these nuclei are differentially sensitive to noxious and non-noxious inputs: Pf was more sensitive to late (200-600 ms latency) high threshold noxious inputs, while VPL was more responsive to early (10-40 ms) low threshold non-noxious inputs. Late, high threshold inputs to VPL were selectively suppressed by systemic morphine and restored by naloxone. Trains of stimuli applied to VPL suppressed the response of 76% of Pf units, to peripheral noxious stimuli but did not inhibit the response of spinal cord dorsal horn units to the same stimuli. This inhibitory effect of VPL on Pf cells was not reversed by systemically administered naloxone. The neural pathways responsible for the VPL suppression of Pf nociception appear to be neither monosynaptic nor mediated through the spinal cord dorsal horn, nor through any single, naloxone-reversible, central opioid process. Nevertheless, this inhibitory effect of VPL stimulation on Pf nociception provides a physiological basis for the analgesic effects of thalamic stimulation on clinically observed deafferentation pain. It also supports the existence of a pain modulating system at the thalamic level comparable, at least in part, with the spinal Gate Control concept.

Afferent Pathways↗

PubMed1996

Fos expression in forebrain afferents to the hypothalamic paraventricular nucleus following swim stress.

The paraventricular nucleus of the hypothalamus (PVN) serves as the origin of the final common pathway in the secretion of glucocorticoid hormones in response to stress. Various stress-related inputs converge upon the cells of the medial parvocellular division of the PVN. These neurons, which synthesize and release corticotropin-releasing hormone, arginine vasopressin, and other secretagogues, are responsible for a cascade of events which culminates in the adrenocorticotropin-induced release of corticosteroids from the adrenal cortex. Previous data have suggested complex afferent regulation of PVN neurons, although the neuronal pathways by which the effects of stress are mediated remain to be fully disclosed. The present experiment sought to identify forebrain areas potentially involved in afferent regulation of the PVN in response to an acute stressor. Discrete injections of the retrograde tracer Fluoro-gold were delivered to the PVN, and rats were subsequently subjected to an acute swim stress. Brains were processed immunocytochemically for the simultaneous detection of the tracer and Fos, the protein product of the immediate early gene c-fos, utilized as a marker for neuronal activation. The majority of Fluoro-gold/Fos labeled neurons were detected in the parastrial nucleus, the medial preoptic area, the anterior hypothalamic area, the dorsomedial hypothalamic nucleus and adjacent posterior hypothalamic area, and, to a lesser extent, the supramammillary nucleus. These findings are discussed in relation to neural pathways mediating activation and inhibition of the hypothalamic-pituitary-adrenocortical axis.

Afferent Pathways↗

PubMed2002

The neuroendocrine basis of social recognition.

All social relationships are dependent on an organism's ability to remember conspecifics. Social memory may be a unique form of memory, critical for reproduction, territorial defense, and the establishment of dominance hierarchies in a natural context. In the laboratory, social memory can be assessed reliably by measuring the reduction in investigation of a familiar partner relative to novel conspecifics. The neurohypophyseal neuropeptides oxytocin and vasopressin have been shown to influence a number of forms of social behavior, including affiliation, aggression, and reproduction. This article reviews vasopressin and oxytocin effects on social cognition, particularly the acquisition and retention of social recognition in rats and mice. Studies in rats have demonstrated that vasopressin in specific neural pathways, such as the lateral septum, is necessary for social recognition. As vasopressin facilitates recall when given after an initial encounter, the peptide appears important for the consolidation not the acquisition of a social memory. Although oxytocin has complex effects on social memory in rats, mice with a null mutation of the oxytocin gene are completely socially amnestic without other cognitive deficits evident. As oxytocin given centrally before but not after the initial encounter restores social recognition in these mutant mice, the neuropeptide appears critical for the acquisition rather than the consolidation phase of memory. Oxytocin's effects on social memory are mediated via a discrete cell population in the medial amygdala. These findings support the hypothesis that vasopressin and oxytocin are essential for social memory, although they appear to influence different cognitive processes and may modulate different neural systems. (c) Elsevier Science.

Animals↗

PubMed2002

Receptors and pathways mediating the effects of prostaglandin E2 on airway tone.

Prostaglandin E(2) (PGE(2)) has complex effects on airway tone, and the existence of four PGE(2) [E-prostanoid (EP)] receptors, each with distinct signaling characteristics, has provided a possible explanation for the seemingly contradictory actions of this lipid mediator. To identify the receptors mediating the actions of PGE(2) on bronchomotor tone, we examined its effects on the airways of wild-type and EP receptor-deficient mice. In conscious mice the administration of PGE(2) increased airway responsiveness primarily through the EP1 receptor, although on certain genetic backgrounds a contribution of the EP3 receptor was detected. These effects of PGE(2) were eliminated by pretreatment with either atropine or bupivacaine and were undetectable in anesthetized mice or in denervated tracheal rings, where only EP2-mediated relaxation of airway smooth muscle was observed. Together, our findings are consistent with a model in which PGE(2) modulates airway tone by activating multiple receptors expressed on various cell populations and in which the relative contribution of these receptors might depend on the expression of modifier alleles. PGE(2)/EP1/EP3-induced airway constriction occurs indirectly through activation of neural pathways, whereas PGE(2)-induced bronchodilation results from direct activation of EP2 receptors on airway smooth muscle. This segregation of EP receptor function within the airway suggests that PGE(2) analogs that selectively activate the EP2 receptor without activating the EP1/EP3 receptors might prove useful in the treatment of asthma.

Anesthesia↗

PubMed1989

[Rabies as a public health problem].

Rabies virus belong to the family Rhabdoviridae; it has a coiled RNA core surrounded by a bullet-shaped envelop, covered with glycoproteins surface projections. After entry into a new host in the bite site, the virus multiplies in muscle cells and it spreads through neural pathways, without stimulating a protective host immune-response. Transmission depends on simultaneous delivery of virus to the salivary gland and the limbic system of the brain, which is the cause of the animal fury and biting tendency. In México, rabies continues to be a serious health and economic problem, and urban rabies still predominates with a large number of human and animal cases recorded yearly. A total of 426 human deaths were reported between 1978 and 1983. Over 9,069 cases of animal rabies were reported in 1986 and 50,000 patients required antirabies postexposure vaccinations. Infected animals can be identified by demonstration of specific fluorescence in brain tissue. A dog or cat which has bitten a human should be captured and observed by a veterinarian for 15 days. The immediate objective of postexposure treatment is to prevent virus from entering and damaging neural tissue, therefore, promptness is essential. All wounds should be thoroughly cleared with soap and water concurrent use of both passive and active immunization provides optimal therapy. Wherever possible, human rather than equine products should be used for passive immunization, and Fuenzalida's nerve tissue rabies vaccine should be used for active protection. Paediatricians should urge parents to caution children attempting to get stray or wild animals as pets. Domestic dogs and cats should be thoroughly vaccinated.

Adolescent↗

PubMed2000

Propagation and neural regulation of calcium waves in longitudinal and circular muscle layers of guinea pig small intestine.

BACKGROUND & AIMS: The relative movements of longitudinal muscle (LM) and circular muscle (CM) and the role that nerves play in coordinating their activities has been a subject of controversy. We used fluorescent video imaging techniques to study the origin and propagation of excitability simultaneously in LM and CM of the small intestine. METHODS: Opened segments of guinea pig ileum were loaded with the Ca(2+) indicator fluo-3. Mucosal reflexes were elicited by lightly depressing the mucosa with a sponge. RESULTS: Spontaneous Ca(2+) waves occurred frequently in LM (1.2 s(-1)) and less frequently in CM (3.2 min(-1)). They originated from discrete pacing sites and propagated at rates 8-9 times faster parallel (LM, 87 mm/s; CM, 77 mm/s) compared with transverse to the long axis of muscle fibers. The presence of Ca(2+) waves in one muscle layer did not affect the origin, rate of conduction, or range of propagation in the other layer. The extent of propagation was limited by collisions with neighboring waves or recently excited regions. Simultaneous excitation of both muscle layers could be elicited by mucosal stimulation of either ascending or descending reflex pathways. Neural excitation resulted in an increase in the frequency of Ca(2+) waves and induction of new pacing sites without eliciting direct coupling between layers. CONCLUSIONS: Localized, spontaneous Ca(2+) waves occur independently in both muscle layers, promoting mixing (pendular or segmental) movements, whereas activation of neural reflexes stimulates Ca(2+) waves synchronously in both layers, resulting in strong peristaltic or propulsive movements.

Animals↗

PubMed2004

Synaptic remodeling in the nucleus ambiguus following vagal-hypoglossal nerve anastomosis in the cat.

We reported recently the occurrence of a massive and selective elimination of synaptic boutons on motoneurons in the dorsal motor nucleus of the vagus (DMV) in the cat following vagal-hypoglossal nerve anastomosis (VHA) [J. Comp. Neurol. 458 (2003) 195]. This study was aimed to explore the synaptic reorganization in the other major nucleus associated with the vagus, namely, the nucleus ambiguus (NA) following the same treatment. In view of the tremendous difference in function, the NA and DMV are considered to be two ideal nuclei for explanatory studies seeking to elucidate how VHA could induce different plasticity of brainstem neurons influenced by the newly reestablished neural pathway. The present results showed that the vagal efferent neurons in the NA had responded to VHA in a different manner compared with those in the DMV. Firstly, the numbers of axon terminals containing round (R), round with dense-cored (R+D), pleomorphic (P) or flattened (F) synaptic vesicles contacting the NA motoneurons were markedly increased at 500-day postoperation, the longest reinnervation interval. The percent increases in the synapse frequency for R, R+D, P and F boutons were 8.6%, 274.4%, 238.3% and 400.0%, respectively. Secondly, the formation of astroglial ensheathment around the motoneurons in the DMV following VHA was not evident in the NA. Another striking difference was the extensive dendritic sprouting of the NA neurons as opposed to the dendritic retraction of the DMV neurons as shown by a significant increase in distal dendrites of NA motoneurons. The different modes of neural remodeling between NA and DMV may be attributed to the unique nature of the two nuclei to structures they normally supply and their different compatibility with the newly innervated target, viz. tongue skeletal musculature.

Anastomosis, Surgical↗

PubMed2000

Nitric oxide is a neurotransmitter in the chloride secretory response to serotonin in rat colon.

BACKGROUND: Serotonin (5-hydroxytryptamine [5-HT]) has been shown to induce chloride secretion through a nonadrenergic/noncholinergic neural pathway, mediated by a 5-HT(3) receptor. We hypothesized that 5-HT(3)-induced Cl(-) secretion is ultimately mediated by nitric oxide (NO). METHODS: Unstripped sheets of rat distal colon were mounted in Ussing chambers and short-circuited. The 5-HT(3) receptor agonist, 2-methyl-5-HT, was added in the absence and presence of the NO synthase inhibitor, L-NAME. Companion studies involved the addition of sodium nitroprusside to tissue that was incubated with or without tetrodotoxin. RESULTS: L-NAME caused a significant reduction in the 2-methyl-5-HT-induced change in circuit current, in a concentration-dependent manner. Sodium nitroprusside caused a change in circuit current over baseline in 5 minutes. The addition of tetrodotoxin did not significantly alter the change in circuit current; however, the apical Cl(-) channel blocker, anthracene-9-carboxylic acid, abolished this response. CONCLUSIONS: Neurally mediated Cl(-) secretion in response to 2-methyl-5-HT is inhibited by an NO synthase inhibitor. Exogenous NO mimics this response, which is unaffected by tetrodotoxin. These data suggest that neurally mediated serotoninergic Cl(-) secretion is, in part, mediated by NO. The ability of exogenous NO to induce a change in circuit current in the presence of tetrodotoxin suggests that NO is a final neurotransmitter in this neural-mucosal reflex and therefore acts directly on the enterocyte to induce secretion.

Animals↗