Myenteric plexus-longitudinal muscle

Z3.3 In Vitro AsKiys for Efficacy. Until the cloning of the opioid receptors isolated tissue preparations, particularly smooth muscle preparations, were used extensively to characterize opioids (see Refs. 131,132 for reviews). The electrically stimulated GPI myenteric plexus-longitudinal muscle and the MVD... 

Begg M, Dale N, Llaudet E, Molleman A, Parsons ME (2002) Modulation of the release of endogenous adenosine by cannabinoids in the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum. Br J Pharmacol 137 1298-1304... 

Mucosal layer Submucosal layer Circular muscle layer Myenteric plexus Longitudinal muscle layer... 

Electrically stimulated longitudinal muscle/myenteric plexus preparations from guinea-pig ileum (LMMP-GPI)... 

Figure 7.1. The effect of ondansetron on contractile responses to 2-methyl-5-HT in the guinea-pig isolated longitudinal muscle myenteric plexus preparation. Symbols indicate control responses (9) or in the presence of ondansetron at 1 x 10- M (O) or 1 x 10 M ( ). Results + S.E.M. of at least four separate observations. Experiments were performed as described by Butler...

Both the parasympathetic and sympathetic nervous systems provide extrinsic gastrointestinal innervation. Parasympathetic stimulation increases muscle contraction of the gut, while sympathetic stimulation inhibits contractions. Stimulation of either a- or 13-adrenoceptors will result in inhibition of contractions. The intramural nervous system consists of a myenteric (Auerbach s) plexus between the circular and longitudinal muscle areas and a submucosal (Meissner s) plexus between the muscularis mucosa and the circular muscle layers. These two plexuses contain stimulatory cholinergic neurons. 

A highly simplified diagram of the intestinal wall and some of the circuitry of the enteric nervous system (ENS). The ENS receives input from both the sympathetic and the parasympathetic systems and sends afferent impulses to sympathetic ganglia and to the central nervous system. Many transmitter or neuromodulator substances have been identified in the ENS see Table 6-1. ACh, acetylcholine AC, absorptive cell CM, circular muscle layer EC, enterochromaffin cell EN, excitatory neuron EPAN, extrinsic primary afferent neuron 5HT, serotonin IN, inhibitory neuron IPAN, intrinsic primary afferent neuron LM, longitudinal muscle layer MP, myenteric plexus NE, norepinephrine NP, neuropeptides SC, secretory cell SMP, submucosal plexus. 

The enteric nervous system (see Chapter 6 Introduction to Autonomic Pharmacology) is composed of interconnected networks of ganglion cells and nerve fibers mainly located in the submucosa (submucosal plexus) and between the circular and longitudinal muscle layers (myenteric plexus). These networks give rise to nerve fibers that connect with the mucosa and deep muscle. Although extrinsic sympathetic and parasympathetic nerves project onto the submucosal and myenteric plexuses, the enteric nervous system can independently regulate gastrointestinal motility and secretion. Afferent fibers present in the mucosa and muscularis connect to cell bodies in the plexuses that mediate local reflexes. 

In addition to in vitro cell models, opioid agonists could induce the rapid endocytosis of the receptor in organo cultures or primary neuronal cultures, and also neurons in vivo. Treatment of longitudinal muscle-myenteric plexus preparation or the primary hippocampal neuron cultures with DAMGO resulted in internalization of the mu opioid receptor [146,147]. Similar observation was obtained with fluorescently labeled opioid peptides Fluo-dermorphin and Fluo-deltorphin [148]. Within 15 min of an intra-peritoneal injection of etorphine, mu opioid receptor immunoreactivity was observed in the endosomal structures of the myenteric neurons of guinea pig ileum [149]. Again, rapid clustering of a spliced variant of mu opioid receptor MOR-1C was observed in the lateral septum of the mouse after intracere-... 

Okwuasaba and Cook (1980) dissected the myenteric plexus and longitudinal muscle free of the underlying circular muscle according to the method of Paton (1957), Paton and Zar (1968) and stimulated the preparation with trains of supramaximal rectangular pulses of 1.0 ms duration at a frequency of 0.2 Hz. 

Gordon, R.K., Gray, R.R., Reaves, C.B., Butler, D.L., and Chiang, P.K. 1992. Induced release of acetylcholine from guinea pig ileum longitudinal muscle-myenteric plexus by anatoxin-a. J Pharmacol Exp Ther 263, 997—1002. 

Paton and Zar (1968) described the dissection of the MP-LMP of the guinea-pig small intestine. This preparation has been invaluable in the study of neurotransmission from the myenteric plexus to the longitudinal smooth muscle, particularly by opioids and cannabinoids, without the confounding effects of the peristaltic reflex. A similar preparation has been used to study neuromuscular transmission to the circular smooth muscle (Izzo et al. 1998). Contractions of MP-LMP induced by electrical field stimulation (EES) were potently inhibited in a concentration-dependent fashion by the cannabinoid receptor agonists CP 55,940, CP 50,556, WIN 55,212-2, nabilone, CP 56,667, A -THC and cannabinol (Coutts and Pertwee 1997 Pertwee 2001). This inhibition was competitively and reversibly antagonised by SR141716A, without any effect on the inhibitory responses to normorphine... 

The activities of the GI tract are controlled locally through a restricted part of the peripheral nervous system called the enteric nervous system (ENS). The ENS is involved in sensorimotor control and consists of both afferent sensory neurons and a number of motor nerves and intemeurons that are organized principally into two nerve plexuses the myenteric (Auerbach s) plexus and the submucosal (Meissner s) plexus. The myenteric plexus, located between the longitudinal and circular muscle layers, plays an important role in the contraction and relaxation of GI smooth muscle. The submucosal plexus is involved with secretory and absorptive functions of the GI epithelium, local blood flow, and neuroimmune activities. The ENS consists of components of the sympathetic and parasympathetic branches of the ANS and has sensory nerve connections through the spinal and nodose ganglia ("see Chapter 37). 

The gastrointestinal (GI) tract is in a continuous contractile, absorptive, and secretory state. The control of this state is complex, with contributions by the muscle itself, local nerves (i.e., the enteric nervous system, ENS), the central nervous system (CNS), and humoral pathways. Of these, perhaps the most important regulator of physiological gut function is the ENS (Figure 37-1), which is an autonomous collection of nerves within the wall of the Gl tract, organized into two connected networks of neurons the myenteric (Auerbach s) plexus, found between the circular and longitudinal muscle layers, and the submucosal (Meissner s) plexus, found below the epithehum. The former is responsible for motor control, while the latter regulates secretion, fluid transport, and vascular flow. 

A) Cumulative concentration effect curves to 5-HT in electrically-stimulated longitudinal muscle myenteric plexus preparation from guinea-pig ileum. ( ) Control biphasic concentration effect curve to 5-HT (O) 5-HT after treatment with 10 pM 5-MeOT. Data from [18]. 

The myenteric plexus lies between the circular and longitudinal layers of smooth muscle and is primarily associated with coordination of motility. The... 

Biser, P.S., Thayne, K.A., Fleming, W.W. and Taylor, D.A., Na, K+ ATPase alpha-subunit isoform distribution and abundance in guinea-pig longitudinal muscle/myenteric plexus after exposure to morphine. Brain Res., 931, 186-193 (2002). 

A ganglion (black) of the myenteric plexus between the longitudinal and circular muscle layers and fibrous septa (orange), which surrounds the ganglion, are resolved at higher magnification. 

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