Role of opioid neurons in the regulation of intestinal peristalsis

1987 ◽  
Vol 253 (2) ◽  
pp. G226-G231 ◽  
Author(s):  
J. R. Grider ◽  
G. M. Makhlouf

The participation of opioid neurons in the regulation of peristalsis was examined in a rat colonic segment that permits separate characterization of the components of the peristaltic reflex (ascending contraction and descending relaxation). Naloxone increased descending relaxation and decreased ascending contraction; opioid peptides [methionine-enkephalin (Met-Enk), dynorphin-13, and morphiceptin] had opposite effects. Naloxone increased, and Met-Enk decreased, vasoactive intestinal peptide (VIP) release during each component of the reflex. The changes in VIP release reinforced the direct effects of naloxone and opioid peptides on circular muscle tone, providing an explanation for the effects of these agents on the two components of the peristaltic reflex. Dynorphin release decreased during descending relaxation and increased during ascending contraction, reflecting corresponding changes in opioid neural activity. Based on these results a model is proposed, according to which a decrease in opioid neural activity during the initial phase (i.e., descending relaxation) results in direct and VIP-mediated decrease in circular muscle tone. Restoration of opioid neural activity during the subsequent phase (i.e., ascending contraction) increases circular muscle tone and reinforces the action of tachykinin and cholinergic motor neurons, which are the direct mediators of ascending contraction.

1987 ◽  
Vol 253 (4) ◽  
pp. G434-G438 ◽  
Author(s):  
J. R. Grider ◽  
A. Arimura ◽  
G. M. Makhlouf

The role of somatostatin neurons in the regulation of peristalsis was examined in segments of rat colon that permit separate characterization of the ascending contraction and descending relaxation components of the peristaltic reflex. Release of somatostatin and vasoactive intestinal peptide (VIP) increased significantly only during descending relaxation. Preincubation of the segment with somatostatin antiserum (final concentration 1:40) decreased VIP release and descending relaxation. Addition of somatostatin (1 nM to 1 microM) augmented VIP release and descending relaxation in a concentration-dependent manner. Together the results implied that the increase in somatostatin release was coupled to, and responsible for, the increase in VIP release, which in turn was responsible for descending relaxation. The results are consistent with the topography of myenteric VIP neurons (which project into circular muscle) and somatostatin neurons (which project caudad within the plexus) and the pharmacological properties of the two peptides. Somatostatin antiserum had no effect on basal VIP release or ascending contraction, indicating that somatostatin neurons were not involved in the regulation of ascending contraction. The study suggests that somatostatin neurons of the myenteric plexus act as facilitatory interneurons in descending pathways.


2001 ◽  
Vol 443 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Hiroyuki Konomi ◽  
Adrian C.B. Meedeniya ◽  
Maria E. Simula ◽  
James Toouli ◽  
Gino T.P. Saccone

2003 ◽  
Vol 284 (2) ◽  
pp. G231-G241 ◽  
Author(s):  
Nick J. Spencer ◽  
Grant W. Hennig ◽  
Terence K. Smith

The role of the longitudinal muscle (LM) layer during the peristaltic reflex in the small and large intestine is unclear. In this study, we have made double and quadruple simultaneous intracellular recordings from LM and circular muscle (CM) cells of guinea pig distal colon to correlate the electrical activities in the two different muscle layers during circumferential stretch. Simultaneous recordings from LM and CM cells (<200 μm apart) at the oral region of the colon showed that excitatory junction potentials (EJPs) discharged synchronously in both muscle layers for periods of up to 6 h. Similarly, at the anal region of the colon, inhibitory junction potentials (IJPs) discharged synchronously in the two muscle layers. Quadruple recordings from LM and CM orally at the same time as from the LM and CM anally revealed that IJPs occurred synchronously in the LM and CM anally at the same time as EJPs in LM and CM located 20 mm orally. Oral EJPs and anal IJPs were linearly related in amplitude between the two muscle layers. Spatiotemporal maps generated from simultaneous video imaging of the movements of the colon, combined with intracellular recordings, revealed that some LM contractions orally could be correlated in time with IJPs in CM cells anally. N ω-nitro-l-arginine (l-NA; 100 μM) abolished the IJP in LM, whereas a prominent l-NA-resistant “fast” IJP was always observed in CM. In summary, in stretched preparations, synchronized EJPs in both LM and CM orally are generated by synchronized firing of many ascending interneurons, which simultaneously activate excitatory motor neurons to both muscle layers. Similarly, synchronized IJPs in both LM and CM anally are generated by synchronized firing of many descending interneurons, which simultaneously activate inhibitory motor neurons to both muscle layers. This synchronized motor activity ensures that both muscles around the entire circumference are excited orally at the same time as inhibited anally, thus producing net aboral propulsion.


2020 ◽  
Author(s):  
Lillian M. Perez ◽  
Aixa Alfonso

ABSTRACTNeural specification can be regulated by one or many transcription factors. Here we identify a novel role for one conserved proneural factor, the bHLH protein HLH-3, implicated in the specification of sex-specific ventral cord motor neurons in C. elegans. In the process of characterizing the role of hlh-3 in neural specification, we document that differentiation of the ventral cord type C neurons, VCs, within their motor neuron class, is dynamic in time and space. Expression of VC class-specific and subclass-specific identity genes is distinct through development and dependent on where they are along the A-P axis (and their position in proximity to the vulva). Our characterization of the expression of VC class and VC subclass-specific differentiation markers in the absence of hlh-3 function reveals that VC fate specification, differentiation, and morphology requires hlh-3 function. Finally, we conclude that hlh-3 cell-autonomously specifies VC cell fate.


2003 ◽  
Vol 284 (5) ◽  
pp. G768-G775 ◽  
Author(s):  
J. R. Grider

A two-compartment, flat-sheet preparation of rat colon was devised, which enabled exclusive measurement of longitudinal muscle activity during the ascending and descending phases of the peristaltic reflex. A previous study using longitudinal muscle strips revealed the operation of an integrated neuronal circuit consisting of somatostatin, opioid, and VIP/pituitary adenylate cyclase-activating peptide (PACAP)/nitric oxide synthase (NOS) interneurons coupled to cholinergic/tachykinin motor neurons innervating longitudinal muscle strips that could lead to descending contraction and ascending relaxation of this muscle layer. Previous studies in peristaltic preparations have also shown that an increase in somatostatin release during the descending phase causes a decrease in Met-enkephalin release and suppression of the inhibitory effect of Met-enkephalin on VIP/PACAP/NOS motor neurons innervating circular muscle and a distinct set of VIP/PACAP/NOS interneurons. The present study showed that in contrast to circular muscle, longitudinal muscle contracted during the descending phase and relaxed during the ascending phase. Somatostatin antiserum inhibited descending contraction and augmented ascending relaxation of longitudinal muscle, whereas naloxone had the opposite effect. VIP and PACAP antagonists inhibited descending contraction of longitudinal muscle and augmented ascending relaxation. Atropine and tachykinin antagonists inhibited descending contraction of longitudinal muscle. As shown in earlier studies, the same antagonists and antisera produced opposite effects on circular muscle. We conclude that longitudinal muscle contracts and relaxes in reverse fashion to circular muscle during the peristaltic reflex. Longitudinal muscle activity is regulated by excitatory VIP/PACAP/NOS interneurons coupled to cholinergic/tachykinin motor neurons innervating longitudinal muscle.


1996 ◽  
Vol 270 (5) ◽  
pp. G778-G782 ◽  
Author(s):  
J. R. Grider ◽  
J. F. Kuemmerle ◽  
J. G. Jin

The intestinal peristaltic reflex can be elicited by mucosal stimulation or circular muscle stretch. Muscle stretch activates extrinsic, whereas mucosal stimulation activates intrinsic calcitonin gene-related peptide (CGRP)-containing sensory neurons. The present study examined the role of 5-hydroxytryptamine (5-HT) in sensory transmission. A three-compartment preparation of rat colon was used that enables separate measurement of sensory transmitters and modulators. Mucosal stimuli (2-8 brush strokes) caused concurrent increase in 5-HT and CGRP release in proportion to the intensity of stimulation. Release of both 5-HT and CGRP occurred exclusively into the central compartment where the stimuli were applied. Exogenous 5-HT caused a concentration-dependent release of CGRP. Release of CGRP induced by exogenous 5-HT or mucosal stimulation was inhibited by selective 5-HT4 and 5-HT1p antagonists but was not affected by 5-HT1A, 5-HT2, and 5-HT3 antagonists. Ascending contraction and descending relaxation of circular muscle measured in the peripheral orad and caudad compartments, respectively, were also selectively inhibited by 5-HT4 and 5-HT1p antagonists added to the central but not peripheral compartments. In contrast, muscle stretch elicited CGRP but not 5-HT release; the ascending contraction and descending relaxation components of the peristaltic reflex induced by muscle stretch were not affected by 5-HT antagonists. We conclude that 5-HT released by mucosal stimulation initiates the peristaltic reflex by activating 5-HT4/5-HT1p receptors on sensory CGRP-containing neurons.


2017 ◽  
Vol 312 (1) ◽  
pp. G1-G14 ◽  
Author(s):  
Terence Keith Smith ◽  
Sang Don Koh

We discuss the role of multiple cell types involved in rhythmic motor patterns in the large intestine that include tonic inhibition of the muscle layers interrupted by rhythmic colonic migrating motor complexes (CMMCs) and secretomotor activity. We propose a model that assumes these motor patterns are dependent on myenteric descending 5-hydroxytryptamine (5-HT, serotonin) interneurons. Asynchronous firing in 5-HT neurons excite inhibitory motor neurons (IMNs) to generate tonic inhibition occurring between CMMCs. IMNs release mainly nitric oxide (NO) to inhibit the muscle, intrinsic primary afferent neurons (IPANs), glial cells, and pacemaker myenteric pacemaker interstitial cells of Cajal (ICC-MY). Mucosal release of 5-HT from enterochromaffin (EC) cells excites the mucosal endings of IPANs that synapse with 5-HT descending interneurons and perhaps ascending interneurons, thereby coupling EC cell 5-HT to myenteric 5-HT neurons, synchronizing their activity. Synchronized 5-HT neurons generate a slow excitatory postsynaptic potential in IPANs via 5-HT7 receptors and excite glial cells and ascending excitatory nerve pathways that are normally inhibited by NO. Excited glial cells release prostaglandins to inhibit IMNs (disinhibition) to allow full excitation of ICC-MY and muscle by excitatory motor neurons (EMNs). EMNs release ACh and tachykinins to excite pacemaker ICC-MY and muscle, leading to the simultaneous contraction of both the longitudinal and circular muscle layers. Myenteric 5-HT neurons also project to the submucous plexus to couple motility with secretion, especially during a CMMC. Glial cells are necessary for switching between different colonic motor behaviors. This model emphasizes the importance of myenteric 5-HT neurons and the likely consequence of their coupling and uncoupling to mucosal 5-HT by IPANs during colonic motor behaviors.


1996 ◽  
Vol 07 (01) ◽  
pp. 101-108 ◽  
Author(s):  
ICHIRO OBANA ◽  
YASUHIRO FUKUI

One role of chaotic neural activity is illustrated by means of computer simulations of an imaginary agent’s goal-oriented behavior. The agent has a simplified neural network with seven neurons and three legs. The neural network consists of one photosensory neuron and three pairs of inter- and motor neurons. The three legs whose movements are governed by the three motor neurons allow the agent to walk in six concentric radial directions on a plane. It is intended that the neural network causes the agent to walk in a direction of greater brightness, to reach finally the most brightly lit place on the plane. The presence of only one sensory neuron has an important meaning. That is, no immediate information on directions of greater brightness is sensed by the agent. In other words, random walking in the manner of trial-and-error problem solving must be involved in the agent’s walking. Chaotic firing of the motor neurons is intended to play a crucial role in generating the random walking. Brief random walking and rapid straight walking in a direction of greater brightness were observed to occur alternately in the computer simulation. Controlled chaos in naturally occurring neural networks may play a similar role.


2000 ◽  
Vol 118 (4) ◽  
pp. A403
Author(s):  
Hiroyuki Konomi ◽  
Adrian C. Meedeniya ◽  
Maria E. Simula ◽  
Jim Toouli ◽  
Gino T. Saccone

1992 ◽  
Vol 262 (4) ◽  
pp. G690-G694 ◽  
Author(s):  
J. R. Grider ◽  
G. M. Makhlouf

The mode of action of gamma-aminobutyric acid (GABA) and the role of myenteric GABA neurons in the regulation of peristalsis were examined in various preparations of rat colonic muscle. GABA had no contractile, relaxant, or modulatory effect on smooth muscle cells isolated from the circular muscle layer. In innervated circular muscle strips, GABA elicited concentration-dependent relaxation accompanied by release of vasoactive intestinal peptide (VIP). Relaxation and VIP release were inhibited by tetrodotoxin and by the GABAA receptor antagonist bicuculline but not by the GABAB receptor antagonist phaclofen. Relaxation was inhibited by the VIP receptor antagonist VIP-(10-28) implying that VIP release was coupled to muscle relaxation. Relaxation was augmented by atropine implying that GABA also activated cholinergic neurons causing release of acetylcholine that attenuated the relaxant response. This pharmacological profile was evident when GABA was released from intrinsic GABA neurons during peristalsis induced by radial stretch. Blockade of GABAA receptors with bicuculline inhibited the descending relaxation mediated by VIP motor neurons and the ascending contraction mediated by cholinergic motor neurons. Stimulation of these receptors with exogenous GABA had the opposite effect. We conclude that on release from myenteric neurons, GABA acts via GABAA receptors on cholinergic and VIP motor neurons responsible for the two components of the peristaltic reflex.


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