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PubMed1996

Electrical activity of the sensory afferent pathway in the enteric nervous system.

In this paper we develop a mathematical model for the electrical activity of the afferent pathway, formed from the coupled primary and secondary sensory neurons. The primary sensory neuron possesses the electrical properties of AH neurons and morphological characteristics of Dogiel type II neurons; the secondary sensory neuron displays the tonic type of electrical behavior and has morphological features of Dogiel type III neurons. Free nerve endings of the mechanoreceptor form the receptive field of the pathway. Based on the general principles of the Hodgkin-Huxley description of excitable cells, the model simulates the following sequence of events: stretch of the receptive field initiates the dendritic potential at the mechanoreceptors; the excitation causes soma action potential development at the primary sensory neuron which is followed by soma action potential generation at the secondary sensory neuron. Numerical calculation have shown that the model is capable of reproducing different electrical patterns within the pathway under normal physiological conditions and after treatment with charybdotoxin, iberiotoxin, tetrodotoxin, omega-conotoxin GVIA, A1-A2 purinoceptor agonists, a protein kinase C activator, and a delta-opioid receptor agonist. Comparison of the computational results with the results of experiments conducted on the neurons of the submucous and myenteric plexi of the small bowel demonstrates their good qualitative and quantitative agreement.

Afferent Pathways↗
PubMed2005

Afferent pathways to the region of the vestibular nuclei that participates in cardiovascular and respiratory control.

Prior experiments have shown that a region of the medial and inferior vestibular nuclei contributes to cardiovascular and respiratory regulation. In addition to labyrinthine inputs, the majority of neurons in this region of the vestibular nuclei receive signals from the skin, muscle, and viscera, although the pathways conveying these nonlabyrinthine inputs to the vestibular nucleus neurons are unknown. To gain further insight into the afferent pathways to this functionally distinct subdivision of the vestibular complex, we combined monosynaptic mapping with viral transneuronal tracing in the ferret. First order afferent projections were defined by retrograde transport of the beta-subunit of cholera toxin (CTbeta), and the extended polysynaptic circuitry was defined in the same animals by injection of a recombinant of pseudorabies virus Bartha (PRV) into the contralateral vestibular nuclei. Neurons containing CTbeta or infected by retrograde transneuronal transport and replication of PRV were distributed throughout the spinal cord, but were 10 times more prevalent in the cervical cord than the lumbar cord. The labeled spinal neurons were most commonly observed in Rexed's laminae IV-VI and the dorsal portions of laminae VII-VIII. Both the CTbeta and PRV injections also resulted in labeling of neurons in all four vestibular nuclei, the prepositus hypoglossi, the reticular formation, the inferior olivary nucleus, the medullary raphe nuclei, the spinal and principal trigeminal nuclei, the facial nucleus, and the lateral reticular nucleus. Following survival times >/=3 days, PRV-infected neurons were additionally present in nucleus solitarius and the gracile and cuneate nuclei. These data show that an anatomical substrate is present for somatosensory and visceral inputs to influence the activity of cells in the autonomic region of the vestibular nuclei and suggest that these signals are primarily transmitted through brainstem relay neurons.

Afferent Pathways↗
PubMed1994

The development of cutaneous afferent pathways in fetal sheep: a structural and functional study.

In this study we have examined the functional and structural development of cutaneous afferent pathways in the fetal sheep hindlimb from 67 to 143 days of gestation. The earliest age at which extracellular discharges could be evoked in dorsal root ganglia and in dorsal horn cells by natural cutaneous stimulation was 75 days. The majority of cells responded to light stroking or indentation of the skin (low threshold) although some cells responded to intense squeezing (high threshold). With increasing gestational age, the majority of cells continued to respond to low threshold stimuli with cells responding to intense mechanical stimuli being recorded less frequently. Dorsal root ganglion cells responding to the cutaneous application of noxious heat (> 45 degrees C) were first observed at 107 days. We have also shown that fibres projecting from dorsal horn cells and presumably entering the spinothalamic tract carry signals at least as far as the mid thoracic spinal cord by 104 days. Ultrastructural studies of the skin revealed bundles of unmyelinated axons located to blood vessels throughout the dermis at 68 days. Innervation of the skin was first observed by silver staining at 75 days when fibres could be seen running along blood vessels in the dermis. With increasing gestational age fibres were seen traversing the dermis to innervate the epidermis as free nerve endings. Wool/hair follicle innervation was first evident at about 100-106 days with only a few follicles being innervated at this age. By 115 days, nerve endings had begun to form circumferential wrappings around follicles and by 134 days lanceolate terminals were observed around the base of the follicles. Biocytin-labelled afferent fibres entered the dorsal horn at 56 days. This initial innervation was sparse but by 76 days there was a marked increase in both the number of afferent fibres entering the dorsal horn and in the extent of their arborisation. Ultrastructural studies revealed that terminals immunoreactive for calcitonin gene-related peptide were present in lamina I as early as 61 days. The period of maximal synaptogenesis and synaptic maturation of this group of terminals appeared to occur between 87-128 days. Therefore the commencement of activation of dorsal horn cells by natural cutaneous stimulation occurs by mid gestation (75 days) in the fetal sheep. This is at the same time or just after peripheral nerves first innervate the skin and about 2 weeks after primary afferent terminals can be identified in the dorsal horn.

Afferent Pathways↗
PubMed1976

The negative potential wave evoked in cuneate nucleus by stimulation of afferent pathways: its origins and susceptibility to inhibition.

1. The negative (N)-wave evoked at various depths in the cuneate nucleus by stimulation of afferents in the ipsilateral forepaw or dorsal column has been studied in the rat. 2. Micro-iontophoretic applications of gamma-aminobutyric acid (GABA) into the vicinity of the recording electrode markedly reduced the amplitude of the negative wave, but only when recordings were made near the base of the cuneate nucleus. Nearer the surface of the medulla, GABA was much less effective. 3. A similar depth distribution obtained for the depression of the negative wave by micro-iontophoretic Mg2+ and enhancement by Ca2+. 4. Depression of the negative wave by conditioning stimulation of the afferent pathway also showed a similar depth distribution. The conditioned depression of the negative wave was most marked during the first 30 ms after the conditioning stimulus and this early depression could be antagonized by iontophoretic (+)-bicuculline methochloride. A lesser degree of conditioned inhibition of the negative wave persisted up to 80-200 ms but this was resistant to (+)-bicuculline methochloride. Thus, conditioned depression of the negative wave appeared to be mediated only in part by a GABA-like transmitter. 5. It is concluded that the negative wave recorded near the base of the cuneate nucleus has some of the predicted properties of a post-synaptic potential. These properties are not seen when the negative wave is recorded more superficially, near the surface of the medulla.

Afferent Pathways↗
PubMed1986

Sensory effects in man of lesions of the posterior columns and of some other afferent pathways.

Clinical observations are presented on the sensory effects of lesions of different afferent pathways of the spinal cord, correlated whenever possible with histological evidence of the location and extent of the lesions. They are based on personal cases and on significant cases in the literature, including posterior column section, other causes of damage to the posterior columns, and cases of commissural myelotomy. It is concluded that the traditional view of the effects of lesions of the posterior columns is correct, but that evidence from cases proved by postmortem examination is still needed. When the information normally supplied by the posterior columns is cut off, primary sensibility for light touch and pressure is not lost, but any kind of discrimination is disturbed. There is also a disturbance in knowledge of movement and position, ataxia, and clumsiness in the use of the hands. These defects greatly affect the palpatory examination of objects and, although they may appear slight on routine neurological examination, they can cause severe disturbances in the activities of daily living. For tactile modalities, a lesion of the spinothalamic complex causes minimal or no defects and a lesion of the posterior columns causes only slight defects, whereas a lesion of both pathways gives rise to total loss of tactile and pressure sensibility in the part of the body served by both pathways. This conclusion is based on 2 cases with combined commissural myelotomy and anterolateral cordotomy. The following disturbances of mechanoreception attributed to lesions of the posterior columns are discussed: lability of threshold, persistence of sensation, tactile and postural hallucinations and temporal and spatial disturbances. In man, lesions of the posterior columns cause an increase in pain, tickle, warmth and cold. Cases are presented with and without lesions of the posterolateral columns in conjunction with lesions of one or both anterolateral columns. As these lesions did not affect sensation and as there was no difference in the sensory state following anterolateral cordotomies with or without involvement of the posterolateral column, it is concluded that lesions of this column have no effect on sensation. Cases with lesions of the anterior two-thirds of the cord are also presented to illustrate the sensory state with only the posterior third of the cord intact. In these cases, tactile and pressure sensibility and knowledge of movement and position are normal.

Animals↗
PubMed1978

[Sources of the afferent pathways of the motor cortex in cats revealed by using the peroxidase method].

By means of the method based on the retrograde axonal transport of exogenic horse-radish peroxidase, there have been stated the sources of afferent pathways of the motor cortex and the structure of neurons sending their axons to the given region. The marked neurons have been found in ipsilateral (SI, SII, Pr, Limb.) and contralateral cortex (MI, Limb.), as well as in the diencephalon (LP, VPL, Hp), the mesencephalon (NR, SN, TM) and the pons (TP). The complex investigation (the peroxidase method and electron microscopy) allowed to get an idea on morphological substrate of disynaptic pathways.

Animals↗
PubMed2001

Afferent pathways of sympathetic skin response in spinal cord: a clinical and electrophysiological study.

BACKGROUND: Sympathetic skin response (SSR) recording is an established test of sudomotor autonomic functions. However, knowledge of its pathways in spinal cord is putative. OBJECTIVE: This study involved subjects with isolated spinal cord lesions to evaluate the afferent pathways of SSR. METHODS: Clinical examination was done according to standard neurological classification of spinal cord injury. Electrophysiological evaluation included: (1) conventional nerve conduction studies to exclude peripheral nerve lesions, (2) scalp somato-sensory-evoked potentials (SEP) with posterior tibial nerve (PTN) stimulation and (3) SSR recording from palm by stimulating supra orbital nerve (SON) at forehead, and PTN at ankle. Subjects with absent SSR in palm to SON stimulation were excluded. In such patients, the afferent tracts were considered abnormal when SSR was absent in palm on stimulation of PTN. RESULTS: Among 37 subjects (age-28.1+/-12.8 years), the afferent tracts of SSR were affected in 13. Sparing of afferent SSR tracts correlated with preservation of bladder sensations (P<0.01). There was no correlation between SSR and SEP. CONCLUSIONS: Spinal cord lesions frequently involve afferent tracts of SSR. Spinal afferents of SSR are closely related with tracts of bladder sensations and are different from pathways for SEP.

Adolescent↗
PubMed1991

Afferent pathway(s) for pharyngeal dilator reflex to negative pressure in man: a study using upper airway anaesthesia.

1. To determine the afferent pathways mediating pharyngeal dilator muscle activation in response to negative airway pressure in man, we recorded genioglossus electromyogram (EMG) activity (via intra-oral bipolar surface electrodes) in response to 500 ms duration pressure stimuli of -15 and -25 cm H2O in normal, conscious, supine subjects relaxed at end-expiration; responses were compared before and after upper airway anaesthesia. 2. Six rectified and integrated EMG responses were bin averaged for pressure stimuli applied with the glottis open (GO) and closed (GC) and to the outside of the face only (controls). Response magnitude was quantified as the ratio of the EMG activity for an 80 ms post-stimulus period (before the subject's reaction time for tongue protrusion) to an 80 ms pre-stimulus period. 3. In eight subjects, upper airway anaesthesia reduced the EMG responses with GC to a level indistinguishable from controls. After anaesthesia, responses with GO remained higher than those with GC. 4. With GC, the mean EMG responses decreased by 43% after selective anaesthesia of the nasal mucosa (trigeminal nerves) in two subjects, 32% after selective anaesthesia of the laryngeal mucosa (superior laryngeal nerves) in six subjects and by 21% after selective anaesthesia of the oropharyngeal mucosa (glossopharyngeal and lingual nerves) in four subjects. 5. We conclude that upper airway afferents mediate pharyngeal dilator muscle activation in response to negative pressure with GC and that subglottal receptors caused the increased activation with GO. With GC, the trigeminal and superior laryngeal nerves mediate an important component of the responses with the glossopharyngeal nerves playing a less important role.

Adult↗
PubMed1983

[Short- and long-term potentiation in the afferent pathways of the hippocampus in the newborn rabbit].

Field potentials were recorded from dendritic and cell body layers of CA1 and dentate regions in newborn rabbits. Responses were evoked by electrical stimulation of the collateral Schaffer system and the perforant path with paired (a 15-100 ms interstimulus interval) and rhythmical stimuli (20-40/c, 3-5 s). Short-term potentiation in the tests with paired stimulation and posttetanic potentiation (up to 3 h) were observed in the CA1 area beginning from the first postnatal day and in the later maturing fascia dentata beginning from 8-10th days, i.e. when neuronal reactions to stimulation of the appropriate afferent pathways first appeared.

Afferent Pathways↗
PubMed1998

Envelope coding in the lateral superior olive. III. Comparison with afferent pathways.

Binaural cues for spatial localization of complex high-frequency sounds are interaural level and time differences (ILDs and ITDs). We previously showed that cells in the lateral superior olive (LSO) are sensitive to ITDs in the envelope of sinusoidally amplitude-modulated (AM) signals up to a modulation frequency of only approximately 800 Hz. To understand the limitations in this ITD-sensitivity, we here compare responses to monaural modulation in LSO and its input pathways, derived from cochlear nucleus and medial nucleus of the trapezoid body. These pathways have marked functional and morphological specializations, suggestive of adaptations for timing. Afferent cell populations were identified on the basis of electrophysiological signatures, and for each population, average firing rate and synchronization to AM tones were compared with auditory-nerve fibers and LSO cells. Except for an increase in modulation gain in some subpopulations, synchronization of LSO afferents was very similar to that in auditory nerve fibers in its dependency on sound pressure level (SPL), modulation depth, and modulation frequency. Distributions of cutoff frequencies of modulation transfer functions were largely coextensive with the distribution in auditory nerve. Group delays, measured from the phase of the response modulation as a function of modulation frequency, showed an orderly dependence on characteristic frequency and cell type and little dependence on SPL. Similar responses were obtained to a modulated broadband carrier. Compared with their afferents, LSO cells synchronized to monaurally modulated stimuli with a higher gain but often over a narrower range of modulation frequencies. Considering the scatter in afferent and LSO cell populations, ipsi- and contralateral responses were well matched in cutoff frequency and magnitude of delays. In contrast to their afferents, LSO cells show a decrease in average firing rate at high modulation frequencies. We conclude that the restricted modulation frequency range over which LSO cells show ITD-sensitivity does not result from loss of envelope information along the afferent pathway but is due to convergence or postsynaptic effects at the level of the LSO. The faithful transmission of envelope phase-locking in LSO afferents is consistent with their physiological and morphological adaptations, but these adaptations are not commensurate with the rather small effects of physiological ITDs reported previously, especially when compared with effects of ILDs. We suggest that these adaptations have evolved to allow a comparison of instantaneous amplitude fluctuations at the two ears rather than to extract interaural timing information per se.

Acoustic Stimulation↗
PubMed2003

Responses and afferent pathways of C(1)-C(2) spinal neurons to gastric distension in rats.

Some evidence shows that the upper cervical spinal cord might play an important role in propriospinal processing as a sensory filter and modulator for visceral afferents. The aims of this study were to determine (1). the responses of C(1)-C(2) spinal neurons to gastric distension and (2). the relative contribution of vagal and spinal visceral afferent pathways for transmission of gastric input to the upper cervical spinal cord. Extracellular potentials of single C(1)-C(2) spinal neurons were recorded in pentobarbital anesthetized male rats. Graded gastric distension (20-80 mm Hg) was produced by air inflation of a latex balloon surgically placed in the stomach. Sixteen percent of the neurons (32/198) responded to gastric distension; 17 neurons were excited and 15 neurons were inhibited by gastric distension. Spontaneous activity of neurons with inhibitory responses was higher than those neurons with excitatory responses (18.1+/-2.7 vs. 3.8+/-1.7 impulses s(-1), p<0.001). Twenty-eight of thirty-two (87.5%) neurons responded to mechanical stimulation of somatic fields on head, neck, ears or shoulder. Most lesion sites of neurons with excitatory responses were found in laminae V, VII; however, neurons with inhibitory responses were in laminae III, IV. Bilateral cervical vagotomy abolished responses of 4/8 neurons tested. Spinal transection at C(6)-C(7) abolished responses of the other four neurons that still responded to gastric distension after bilateral vagotomy. Results of these data supported the concept that a group of C(1)-C(2) spinal neurons might play a role in processing sensory information from the stomach that travels in vagal and spinal visceral afferent fibers.

Afferent Pathways↗
PubMed1995

The primary afferent pathway of extraocular muscle proprioception in the pigeon.

Recent physiological experiments in our laboratory suggest that extraocular muscle proprioceptive signals are involved in oculomotor control in the pigeon [e.g., Knox and Donaldson (1993) Proc. R. Soc. Lond. B 253, 77-82]; the present results provide information about the primary afferent pathway involved in these actions. In other physiological experiments [Hayman et al. (1993) Proc. R. Soc. Lond. B 254, 115-122] we have shown that extraocular muscle afferent signals modify vestibularly driven neck reflexes in the pigeon; the present results suggest an anatomical substrate for these effects. The localization of the cell bodies and of the central terminations of afferent fibres from the extraocular muscles of the pigeon was examined using transport of horseradish peroxidase. The results showed that primary afferent cell somata subserving extraocular muscle proprioception are located within the ipsilateral trigeminal ganglion. The presence of heavily labelled brainstem neurons reported in a previous study [Eden et al. (1982) Brain Res. 237, 15-21] was confirmed; however, these cells were shown to be accessory abducens motoneurons innervating the quadratus muscle, and presumably the pyramidalis muscle also, and not proprioceptive afferent somata as had been suggested. The central projections of extraocular muscle afferent neurons were found consistently in a restricted area of the external cuneate nucleus. This is in contrast to findings in a number of mammals in which the terminal label has been seen to cluster in portions of the spinal trigeminal nucleus. The presence of a lateral trigeminal tract in the pigeon, through which the afferent axons course, which terminates exclusively in the ventral portion of the external cuneate nucleus may explain this finding.

Afferent Pathways↗
PubMed1982

Histochemical localization of cytochrome oxidase in the hippocampus: correlation with specific neuronal types and afferent pathways.

Cytochrome oxidase was histochemically localized in the hippocampus and dentate gyrus of various species of mammals. The most intense staining was observed within stratum moleculare of areas CA1-3 and the outer molecular layer of the dentate gyrus, as well as the somatic and basal dendritic layers of CA3. These regions correspond to the synaptic terminal fields of major excitatory afferent pathways to the hippocampus. The somata of CA3 pyramidal cells and various interneurons were more intensely stained than CA1 pyramidal cells and dentate granule cells, and these levels appeared to correlate positively with their reported rates of spontaneous firing. At the electron-microscopic level, the highest concentrations of densely reactive mitochondria were localized within the distal apical dendritic profiles of principal cells (granule and pyramidal) and certain interneurons (pyramidal basket and stratum pyramidale interneurons). The specific layers in which these structures were found are known to receive intense excitatory input from the perforant pathway. High concentrations of reactive mitochondria were also observed within the somata and proximal dendrites of CA3 pyramidal cells and various interneurons, confirming our light-microscopic observations. These results demonstrated that not only can soma and dendrites of the same cell have disparate but distinct levels of cytochrome oxidase activity, but the pattern of reactivity within a neuron's apical and basal dendrites, or even within specific dendritic segments of the same dendrite can be quite different. While the levels of somatic reactivity correlate with reported levels of spontaneous and/or synaptic activity, the degree of dendritic and somatic staining appeared to be more closely related to the intensity of convergent and/or pathway-specific excitatory synaptic input.

Afferent Pathways↗
PubMed1994

Morphological and electrophysiological analysis of the peripheral and central afferent pathways from the clitoris of the cat.

Afferent neurons projecting to the clitoris of the cat were identified by WGA-HRP tracing in the S1 and S2 dorsal root ganglia. An average of 433 cells were identified on each side of the animal. 85% and 15% of the labeled cells were located in the S1 and S2 dorsal root ganglia, respectively. The average cross sectional area of clitoral afferent neuron profiles was 1,479 +/- 627 micron2. Unilateral transection of the pudendal nerve reduced the number of labeled cells to 1% of that on the control side. Central projections of clitoral afferents were identified in the lumbo-sacral segments (L7-S3) of the spinal cord. HRP labeled fibers were located in the marginal zone on the medial side of dorsal horn and extended into the dorsal half of the dorsal gray commissure. Electrophysiological recordings detected axonal volleys in the pudendal nerve and S1 dorsal root in response to electrical stimulation (threshold, 1-4 V) of the clitoral surface. Estimated axonal conduction velocities at the two sites ranged from 7-27 m/s and 0.6-30 m/s, respectively. Multi-unit recordings from dorsal roots in the lumbo-sacral segments revealed that non-noxious pressure stimulation of the clitoris evoked discharges in the S1 dorsal root. Small increases were also detected in the S2 and L7 roots. Single unit discharges recorded from S1 dorsal roots were activated by electrical stimulation of the clitoral surface at thresholds of 0.6-1.2 V and latencies of 1.5-1.8 ms (estimated conduction velocities of 24-30 m/s.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed2005

Rectal hyposensitivity: a disorder of the rectal wall or the afferent pathway? An assessment using the barostat.

OBJECTIVES: Rectal hyposensitivity (RH) relates to a diminished perception of rectal distension. Diagnosis on the basis of abnormal threshold volumes on balloon distension alone may be inaccurate due to the influence of differing rectal wall properties. The aim of this study was to investigate whether RH was actually due to impaired afferent nerve function or whether it could be secondary to abnormalities of the rectal wall. METHODS: A total of 50 patients were referred consecutively to a tertiary referral unit for physiologic assessment of constipation (Rome II criteria), 25 of whom had associated fecal incontinence. Thirty patients had RH (elevated threshold volumes on latex balloon distension), and 20 patients had normal rectal sensation (NS). Results were compared with those obtained in 20 healthy volunteers (HV). All subjects underwent standard anorectal physiologic investigation, and assessment of rectal compliance, adaptive response to isobaric distension at urge threshold, and postprandial rectal response, using an electromechanical barostat. RESULTS: Mean rectal compliance was significantly elevated in patients with RH compared to NS and HV (p < 0.001). However, 16 patients with RH (53%) had normal compliance. Intensity of the urge to defecate during random phasic isobaric distensions was significantly reduced in patients with RH compared to NS and HV (p < 0.001). The adaptive response at urge threshold was reduced in patients with RH compared to NS and HV (p < 0.001), although spontaneous adaptation at operating pressure was similar in all three groups studied (p= 0.3). Postprandially, responses were similar between groups. CONCLUSIONS: In patients found to have RH on simple balloon distension, impaired perception of rectal distension may be partly explained in one subgroup by abnormal rectal compliance. However, a second subgroup exists with normal rectal wall properties, suggestive of a true impairment of the afferent pathway. The barostat has an important role in the identification of these subgroups of patients.

Adult↗
PubMed1994

Endogenous cholecystokinin stimulates pancreatic enzyme secretion via vagal afferent pathway in rats.

BACKGROUND/AIMS: Recently we showed that doses of cholecystokinin octapeptide (CCK-8) that produce physiological plasma CCK levels act via stimulation of afferent vagal pathway to mediate pancreatic enzyme secretion. In this study we investigated if endogenous CCK also acts via similar pathway. METHODS: In anesthetized rats, plasma CCK levels were elevated by diversion of bile pancreatic juice and duodenal casein feeding. The effects of acute vagotomy as well as that of chemical ablation of the afferent vagal pathway on pancreatic enzyme secretion evoked by increased endogenous plasma CCK levels were investigated. RESULTS: Diversion of bile pancreatic juice elevated plasma CCK levels from a basal level of 0.6 +/- 0.1 pmol/L to 8.9 +/- 2.1 pmol/L and caused a more than twofold increase in pancreatic protein secretion. Similar increases in plasma CCK levels and pancreatic secretion were observed with duodenal administration of casein. Vagotomy or perivagal application of capsaicin, a sensory neurotoxin, abolished increases in pancreatic secretion but not plasma CCK levels in response to diversion of bile pancreatic secretion or duodenal administration of casein. In contrast, pancreatic protein responses to 2-deoxy-D-glucose, a central vagal stimulant, remained intact in rats with perivagal capsaicin treatment indicating capsaicin did not affect efferent vagal function. CONCLUSIONS: Endogenous CCK under physiological conditions act via stimulation of vagal afferent pathway to mediate pancreatic enzyme secretion.

Afferent Pathways↗
PubMed1995

Secretin at physiological doses inhibits gastric motility via a vagal afferent pathway.

Secretin is an important modulator of gastric motility. In this study, we investigated the site(s) and mechanism(s) of action of secretin to inhibit gastric motility, using an in vivo rat model. Intragastric pressure response to graded doses of secretin was recorded in anesthetized rats by a balloon attached to a catheter passed through an incision in the duodenum into the body of the stomach. The intragastric pressure was set at 10 cmH2O with balloon distension. Intravenous infusion of secretin (1.4, 2.8, 5.6, 11.2, and 22.4 pmol.kg-1.h-1) decreased intragastric pressure in a dose-dependent manner. The threshold dose was 2.8 pmol.kg-1.h-1, and the effective dose at 50% (ED50) was 5.6 pmol.kg-1.h-1, which produced physiological levels of plasma secretin. Pretreatment with hexamethonium (10 mg/kg) markedly reduced gastric motor response to secretin (5.6 pmol.kg-1.h-1). Bilateral truncal vagotomy also significantly diminished gastric motor responses to secretin. In contrast, secretin (5.6 pmol.kg-1.h-1) had no effect on gastric contraction evoked by electrical vagal stimulation (1.25-5 Hz) or carbachol (10(-6) to 3 x 10(-5) M). These observations indicate that physiological concentrations of secretin act via stimulation of presynaptic cholinergic neurons in a vagally mediated pathway. In subsequent studies, we demonstrated that perivagal treatment 4 days before with the sensory neurotoxin, capsaicin, abolished gastric motor response to secretin but did not affect contraction evoked by electrical vagal stimulation. Similarly, we also showed that gastroduodenal application of capsaicin for 30 min also markedly reduced gastric response to secretin. These observations indicate that physiological doses of secretin act on vagal afferent pathways originating from the gastroduodenal mucosa to induce gastric relaxation.

Afferent Pathways↗