Mucosal stimulation activates secretomotor neurons via long myenteric pathways in guinea pig ileum

2007 ◽  
Vol 292 (2) ◽  
pp. G608-G614 ◽  
Author(s):  
David E. Reed ◽  
Stephen Vanner
Keyword(s):  
Guinea Pig ◽  
Sensory Neurons ◽  
Sensory Nerve ◽  
Intestinal Secretion ◽  
Distal Portion ◽  
Excitatory Postsynaptic Potential ◽  
Stimulus Pulse ◽  
Stimulus Site ◽  
Secretomotor Neurons

This study examined whether mucosal stimulation activates long secretomotor neural reflexes and, if so, how they are organized. The submucosa of in vitro full thickness guinea pig ileal preparations was exposed in the distal portion and intracellular recordings were obtained from electrophysiologically identified secretomotor neurons. Axons in the intact mucosa of the oral segment were stimulated by a large bipolar stimulating electrode. In control preparations, a single stimulus pulse evoked a fast excitatory postsynaptic potential (EPSP) in 86% of neurons located 0.7–1.0 cm anal to the stimulus site. A stimulus train evoked multiple fast EPSPs, but slow EPSPs were not observed. To examine whether mucosal stimulation specifically activated mucosal sensory nerve terminals, the mucosa/submucosa was severed from the underlying layers and repositioned. In these preparations, fast EPSPs could not be elicited in 89% of cells. Superfusion with phorbol dibutyrate enhanced excitability of sensory neurons and pressure-pulse application of serotonin to the mucosa increased the fast EPSPs evoked by mucosal stimulation, providing further evidence that sensory neurons were involved. To determine whether these reflexes projected through the myenteric plexus, this plexus was surgically lesioned between the stimulus site and the impaled neuron. No fast EPSPs were recorded in these preparations following mucosal stimulation whereas lesioning the submucosal plexus had no effect. These results demonstrate that mucosal stimulation triggers a long myenteric pathway that activates submucosal secretomotor neurons. This pathway projects in parallel with motor and vasodilator reflexes, and this common pathway may enable coordination of intestinal secretion, blood flow, and motility.

Capsaicin-sensitive afferent nerves activate submucosal secretomotor neurons in guinea pig ileum

1995 ◽  
Vol 269 (2) ◽  
pp. G203-G209 ◽  
Author(s):  
S. Vanner ◽  
W. K. MacNaughton
Keyword(s):  
Guinea Pig ◽  
Ion Transport ◽  
Short Circuit ◽  
Ussing Chamber ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Guinea Pig Ileum ◽  
Secretomotor Neurons

This study examined whether capsaicin-sensitive sensory nerves regulate intestinal ion transport using both Ussing chamber and intracellular recording techniques in in vitro submucosal preparations from the guinea pig ileum. In Ussing chamber studies, serosal application of capsaicin (20 nM-20 microM) evoked a biphasic dose-dependent increase in short-circuit current (Isc) (maximal effective concentration 200 nM and 2 microM, respectively). In chloride-free buffer, capsaicin responses were significantly reduced. Capsaicin evoked little or no response when extrinsic sensory nerve fibers had been surgically removed and tetrodotoxin and low-calcium and high-magnesium solutions blocked responses to capsaicin. In epithelial preparations devoid of submucosal neurons, capsaicin had virtually no effect, suggesting that responses evoked by capsaicin-sensitive nerves result from activation of submucosal secretomotor neurons. Intracellular recordings from single submucosal neurons demonstrated that superfusion with capsaicin (2 microM) depolarized neurons with an associated decreased conductance. Depolarizations were completely desensitized when capsaicin was reapplied, but synaptic inputs were unaffected. This study suggests that capsaicin-sensitive nerves can regulate ion transport in the gastrointestinal tract by release of neurotransmitter(s) that activate submucosal secretomotor neurons.

Sensory peptide neurotransmitters mediating mucosal and distension evoked neural vasodilator reflexes in guinea pig ileum

2005 ◽  
Vol 289 (5) ◽  
pp. G785-G790 ◽  
Author(s):  
D. Patton ◽  
M. O'Reilly ◽  
S. Vanner
Keyword(s):  
Guinea Pig ◽  
Sensory Neurons ◽  
Myenteric Plexus ◽  
Distal Portion ◽  
Neural Mechanisms ◽  
Combined Application ◽  
Balloon Distension ◽  
Descending Interneurons ◽  
Sensory Neural

The aim was to determine the role CGRP and/or tachykinins released from sensory neural mechanisms in enteric neural vasodilator pathways. These pathways project through the myenteric plexus to submucosal vasodilator neurons. Submucosal arterioles were exposed in the distal portion of an in vitro combined submucosal-myenteric guinea pig ileal preparation, and dilation was monitored with videomicroscopy. Vasodilator neural reflexes were activated by gently stroking the mucosa with a fine brush or by distending a balloon placed beneath the flat-sheet preparation in the proximal portion. Dilations evoked by mucosal stroking were inhibited 64% by the CGRP 8–37 and 37% by NK3 (SR 142801) antagonists. When the two antagonists were combined with hexamethonium, only a small vasodilation persisted. Balloon distension-evoked vasodilations were inhibited by NK3 antagonists (66%) but were not altered by CGRP 8–37. In preparations in which myenteric descending interneurons were directly activated by electrical stimulation, combined application of CGRP 8–37 and the NK antagonists had no effect. Stimulation of capsaicin sensitive nerves in the myenteric plexus did not activate these vasodilator reflexes. These findings suggest that mucosal-activated reflexes result from the release of CGRP and tachykinins from enteric sensory neurons. Distension-evoked responses were significantly blocked by NK3 antagonists, suggesting that stretch activation of myenteric sensory neurons release tachykinins that activate NK3 receptors on myenteric vasodilator pathways.

scholarly journals The Effects of Polarizing Current on Nerve Terminal Impulses Recorded from Polymodal and Cold Receptors in the Guinea-pig Cornea

2002 ◽  
Vol 120 (3) ◽  
pp. 395-405 ◽  
Author(s):  
Richard W. Carr ◽  
Svetlana Pianova ◽  
James A. Brock
Keyword(s):  
Guinea Pig ◽  
Nerve Terminal ◽  
Sensory Nerve ◽  
Outward Current ◽  
Nerve Terminals ◽  
Functional Difference ◽  
Inward Current ◽  
Cold Receptor ◽  
Cold Receptors

It was reported recently that action potentials actively invade the sensory nerve terminals of corneal polymodal receptors, whereas corneal cold receptor nerve terminals are passively invaded (Brock, J.A., S. Pianova, and C. Belmonte. 2001. J. Physiol. 533:493–501). The present study investigated whether this functional difference between these two types of receptor was due to an absence of voltage-activated Na+ conductances in cold receptor nerve terminals. To address this question, the study examined the effects of polarizing current on the configuration of nerve terminal impulses recorded extracellularly from single polymodal and cold receptors in guinea-pig cornea isolated in vitro. Polarizing currents were applied through the recording electrode. In both receptor types, hyperpolarizing current (+ve) increased the negative amplitude of nerve terminal impulses. In contrast, depolarizing current (−ve) was without effect on polymodal receptor nerve terminal impulses but increased the positive amplitude of cold receptor nerve terminal impulses. The hyperpolarization-induced increase in the negative amplitude of nerve terminal impulses represents a net increase in inward current. In both types of receptor, this increase in inward current was reduced by local application of low Na+ solution and blocked by lidocaine (10 mM). In addition, tetrodotoxin (1 μM) slowed but did not reduce the hyperpolarization-induced increase in the negative amplitude of polymodal and cold nerve terminal impulses. The depolarization-induced increase in the positive amplitude of cold receptor nerve terminal impulses represents a net increase in outward current. This change was reduced both by lidocaine (10 mM) and the combined application of tetraethylammomium (20 mM) and 4-aminopyridine (1 mM). The interpretation is that both polymodal and cold receptor nerve terminals possess high densities of tetrodotoxin-resistant Na+ channels. This finding suggests that in cold receptors, under normal conditions, the Na+ conductances are rendered inactive because the nerve terminal region is relatively depolarized.

scholarly journals Human osteoarthritic synovial fluid increases excitability of mouse dorsal root ganglion sensory neurons: an in-vitro translational model to study arthritic pain

Rheumatology ◽  
2019 ◽  
Author(s):  
Sampurna Chakrabarti ◽  
Deepak R Jadon ◽  
David C Bulmer ◽  
Ewan St. John Smith
Keyword(s):  
Dorsal Root Ganglion ◽  
Knee Pain ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Drug Targets ◽  
Transient Receptor Potential ◽  
Sensory Nerve ◽  
Resting Membrane Potential ◽  
Translational Model

Abstract Objectives Knee OA is a leading global cause of morbidity. This study investigates the effects of knee SF from patients with OA on the activity of dorsal root ganglion sensory neurons that innervate the knee (knee neurons) as a novel translational model of disease-mediated nociception in human OA. Methods Dissociated cultures of mouse knee neurons were incubated overnight or acutely stimulated with OA-SF (n = 4) and fluid from healthy donors (n = 3, Ctrl-SF). Electrophysiology and Ca2+-imaging determined changes in electrical excitability and transient receptor potential channel function, respectively. Results Incubation with OA-SF induced knee neuron hyperexcitability compared to Ctrl-SF: the resting membrane potential significantly increased (F(2, 92) = 5.6, P = 0.005, ANOVA) and the action potential threshold decreased (F(2, 92) = 8.8, P = 0.0003, ANOVA); TRPV1 (F(2, 445) = 3.7, P = 0.02) and TRPM8 (F(2, 174) = 11.1, P < 0.0001, ANOVA) channel activity also increased. Acute application of Ctrl-SF and OA-SF increased intracellular Ca2+ concentration via intra- and extracellular Ca2+ sources. Conclusion Human OA-SF acutely activated knee neurons and induced hyperexcitability indicating that mediators present in OA-SF stimulate sensory nerve activity and thereby give rise to knee pain. Taken together, this study provides proof-of-concept for a new method to study the ability of mediators present in joints of patients with arthritis to stimulate nociceptor activity and hence identify clinically relevant drug targets for treating knee pain.

Sa1741 Vpac1 Receptors Localised to Cholinergic Secretomotor Neurons Regulate Intestinal Secretion in Guinea-Pig Jejunum

2013 ◽  
Vol 144 (5) ◽  
pp. S-296
Author(s):  
Candice Fung ◽  
Jaime Pei Pei Foong ◽  
Laura J. Parry ◽  
Joel C. Bornstein
Keyword(s):  
Guinea Pig ◽  
Intestinal Secretion ◽  
Pig Jejunum ◽  
Secretomotor Neurons

scholarly journals 5-HT1A, SST1, and SST2receptors mediate inhibitory postsynaptic potentials in the submucous plexus of the guinea pig ileum

2010 ◽  
Vol 298 (3) ◽  
pp. G384-G394 ◽  
Author(s):  
Jaime Pei Pei Foong ◽  
Laura J. Parry ◽  
Rachel M. Gwynne ◽  
Joel C. Bornstein
Keyword(s):  
Confocal Microscopy ◽  
Guinea Pig ◽  
Close Contact ◽  
Neural Pathways ◽  
Rt Pcr ◽  
Guinea Pig Ileum ◽  
Submucous Plexus ◽  
Adrenoceptor Antagonist ◽  
Secretomotor Neurons

Vasoactive intestinal peptide (VIP) immunoreactive neurons are important secretomotor neurons in the submucous plexus. They are the only submucosal neurons to receive inhibitory inputs and exhibit both noradrenergic and nonadrenergic inhibitory synaptic potentials (IPSPs). The former are mediated by α2-adrenoceptors, but the receptors mediating the latter have not been identified. We used standard intracellular recording, RT-PCR, and confocal microscopy to test whether 5-HT1A, SST1, and/or SST2receptors mediate nonadrenergic IPSPs in VIP submucosal neurons in guinea pig ileum in vitro. The specific 5-HT1Areceptor antagonist WAY 100135 (1 μM) reduced the amplitude of IPSPs, an effect that persisted in the presence of the α2-adrenoceptor antagonist idazoxan (2 μM), suggesting that 5-HT might mediate a component of the IPSPs. Confocal microscopy revealed that there were many 5-HT-immunoreactive varicosities in close contact with VIP neurons. The specific SSTR2antagonist CYN 154806 (100 nM) and a specific SSTR1antagonist SRA 880 (3 μM) each reduced the amplitude of nonadrenergic IPSPs and hyperpolarizations evoked by somatostatin. In contrast with the other antagonists, CYN 154806 also reduced the durations of nonadrenergic IPSPs. Effects of WAY 100135 and CYN 154806 were additive. RT-PCR revealed gene transcripts for 5-HT1A, SST1, and SST2receptors in stripped submucous plexus preparations consistent with the pharmacological data. Although the involvement of other neurotransmitters or receptors cannot be excluded, we conclude that 5-HT1A, SST1, and SST2receptors mediate nonadrenergic IPSPs in the noncholinergic (VIP) secretomotor neurons. This study thus provides the tools to identify functions of enteric neural pathways that inhibit secretomotor reflexes.

Differential Thermosensitivity of Sensory Neurons in the Guinea Pig Trigeminal Ganglion

2003 ◽  
Vol 90 (4) ◽  
pp. 2219-2231 ◽  
Author(s):  
C. Cabanes ◽  
F. Viana ◽  
C. Belmonte
Keyword(s):  
Guinea Pig ◽  
Sensory Neurons ◽  
Trigeminal Ganglion ◽  
Input Resistance ◽  
Membrane Properties ◽  
Cold Sensitivity ◽  
Inward Rectification ◽  
Nerve Terminals ◽  
Membrane Hyperpolarization

Intracellular recordings were employed to study the effects of temperature on membrane properties and excitability in sensory neurons of the intact guinea pig trigeminal ganglion (TG) maintained in vitro. Neurons were classified according to the shape and duration of the action potential into F (short-duration, fast spike) and S (long duration, slow spike with a “hump”) types. Most type F (33/34) neurons had axons with conduction velocities >1.5 m/s, while only 30% (6/23) of type S neurons reached these conduction speeds suggesting differences in myelination. Cooling reduced axonal conduction velocity and prolonged spike duration in both neuronal types. In F-type neurons with strong inward rectification. cooling also increased the excitability, augmenting the input resistance and reducing the current firing threshold. These effects were not observed in S-type neurons lacking inward rectification. In striking contrast to results obtained in cultured TG neurons, cooling or menthol did not induce firing in recordings from the acutely isolated ganglion. However, after application of submillimolar concentrations (100 μM) of the potassium channel blocker 4-aminopyridine (4-AP), 29% previously unresponsive neurons developed cold sensitivity. An additional 31% developed ongoing activity that was sensitive to temperature. Only neurons with strong inward rectification (mostly F-type) became thermosensitive. Cooling- and 4-AP–evoked firing were insensitive to intracellular application of 4-AP or somatic membrane hyperpolarization, suggesting that their action was most prominent at the level of the axon. The lack of excitatory actions of low temperature in the excised intact ganglion contrasts with the impulse discharges induced by cooling in trigeminal nerve terminals of the same species, suggesting a critical difference between cold-transduction mechanisms at the level of the nerve terminals and the soma.

scholarly journals Prostaglandin D2 and the role of the DP1, DP2 and TP receptors in the control of airway reflex events

2014 ◽  
Vol 45 (4) ◽  
pp. 1108-1118 ◽  
Author(s):  
Sarah A. Maher ◽  
Mark A. Birrell ◽  
John J. Adcock ◽  
Michael A. Wortley ◽  
Eric D. Dubuis ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Receptor Agonist ◽  
Sensory Nerve ◽  
Sensory Nerves ◽  
Vagal Afferents ◽  
Prostaglandin D2 ◽  
Airway Reflex ◽  
Guinea Pig Model

Prostaglandin D2 (PGD2) causes cough and levels are increased in asthma suggesting that it may contribute to symptoms. Although the prostaglandin D2 receptor 2 (DP2) is a target for numerous drug discovery programmes little is known about the actions of PGD2 on sensory nerves and cough.We used human and guinea pig bioassays, in vivo electrophysiology and a guinea pig conscious cough model to assess the effect of prostaglandin D2 receptor (DP1), DP2 and thromboxane receptor antagonism on PGD2 responses.PGD2 caused cough in a conscious guinea pig model and an increase in calcium in airway jugular ganglia. Using pharmacology and receptor-deficient mice we showed that the DP1 receptor mediates sensory nerve activation in mouse, guinea pig and human vagal afferents. In vivo, PGD2 and a DP1 receptor agonist, but not a DP2 receptor agonist, activated single airway C-fibres. Interestingly, activation of DP2 inhibited sensory nerve firing to capsaicin in vitro and in vivo.The DP1 receptor could be a therapeutic target for symptoms associated with asthma. Where endogenous PGD2 levels are elevated, loss of DP2 receptor-mediated inhibition of sensory nerves may lead to an increase in vagally associated symptoms and the potential for such adverse effects should be investigated in clinical studies with DP2 antagonists.

scholarly journals 962 Cortistatin Inhibits Intestinal Secretion in the Guinea Pig Ileum In Vitro

2010 ◽  
Vol 138 (5) ◽  
pp. S-141
Author(s):  
Sumei Liu ◽  
Wei Ren ◽  
Jackie D. Wood
Keyword(s):  
Guinea Pig ◽  
Intestinal Secretion ◽  
Guinea Pig Ileum
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