Myenteric plexus, effect

Cosentino M, Marino F, De Ponti F et al (1995) Tonic modulation of neurotransmitter release in the guinea-pig myenteric plexus effect of mu and kappa opioid receptor blockade and of chronic sympathetic denervation. Neurosci Lett 194 185-8 Costa M, Majewski H (1988) Facilitation of noradrenaline release from sympathetic nerves through activation of ACTH receptors, B-adrenoceptors and angiotensin II receptors. Br J Pharmacol 95 993-1001... 

Pertwee RGS, L. A. Elrick DB, Mechoulam R, Corbett AD. Inhibitory effects of certain enantiomeric cannabinoids in the mouse vas deferens and the myenteric plexus preparation of guinea-pig small intestine. Br J Pharmacol 1992 105 980-984. 

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...

As previously noted, opioids have significant constipating effects (see Chapter 31). They increase colonic phasic segmenting activity through inhibition of presynaptic cholinergic nerves in the submucosal and myenteric plexuses and lead to increased colonic transit time and fecal water absorption. They also decrease mass colonic movements and the gastrocolic reflex. Although all opioids have antidiarrheal effects, central nervous system effects and potential for addiction limit the usefulness of most. 

Garaulet, J.V., Laorden, M.L., Milanes, M.V. Effect of chronic administration of dihydropyridine Ca2+ channel ligands on sufentanil-induced tolerance to p- and K-opioid agonists in the guinea pig ileum myenteric plexus, Regulatory Peptides 1996, 63, 1-8. 

Ordinarily, defecation results from the defecation reflexes, which can be described as follows. When the feces enter the rectum, distension of the rectal wall initiates afferent signals that spread through the myenteric plexus to initiate peristaltic waves in the descending colon, sigmoid, and rectum, forcing feces toward the anus. As the peristaltic wave approaches the anus, the internal anal sphincter is inhibited by the usual phenomenon of receptive relaxation, and if the external anal sphincter is relaxed, defecation will occur. This overall effect is the intrinsic defecation reflex of the colon itself. 

Cannabinoid and endocannabinoid-induced synaptic depression is observed in both the peripheral nervous system and the CNS. Indeed, A9-THC inhibition of transmitter release was first demonstrated in mouse vas deferens (Graham et al. 1974), and further evidence for presynaptic inhibition has been obtained using this preparation (Ishac et al. 1996 Pertwee and Fernando 1996) and in the myenteric plexus (Coutts and Pertwee 1997 Kulkami-Narla and Brown 2000). In addition, anandamide was first characterized as an EC based on its actions in the mouse vas deferens (Devane et al. 1992). Subsequently, CB1 receptor-mediated inhibition of release of several neurotransmitters has been documented in various regions of the PNS (see Szabo and Schlicker 2005 for review). Cannabinoids also inhibit neural effects on contraction in the ileum (Croci et al. 1998 Lopez-Redondo et al. 1997), although it is not clear that this is effect involves direct inhibition of neurotransmitter release (Croci et al. 1998). The CB1 receptor has been localized to enteric neurons, and thus the effect on ileum certainly involves actions on these presynaptic neurons. In addition, anandamide produces ileal relaxation via a non-CBl, non-CB2-mediated mechanism (Mang et al. 2001). 

Kilbinger H, Gebauer A, Hass J et al. (1995) Benzimidazoles and renzapride facilitate acetylcholine release from guinea pig myenteric plexus via 5-HT4receptors. Naunyn-Schmiedeberg s Arch Pharmacol 351 229-236 Koelle GB, Koelle ES, Friedenwald JD (1950) The effect of inhibition of specific and non-specific cholinesterase on the motility of the isolated ileum. J Pharm Exp Ther 100 180-191... 

Q6 Loperamide hydrochloride is an opioid. The starting dose will be 4 mg, which can be reduced to 2 mg, three times a day for five days if necessary. Opioids act on // opiate receptors in the myenteric plexus of the intestine and may modulate acetylcholine release to reduce peristalsis. They trigger mucosal transport of ions and water out of the lumen and cause a reduction in secretion. The absorption of fluid and electrolytes is increased since the stool remains in the colon for a longer period. Loperamide does not produce sedation or other central effects associated with opiates, since it does not cross the blood-brain barrier. 

Anadon, A., Martinez-Larranaga, M.R. (1985). Effects of crotoxin on autonomic neuromuscular transmission in the guinea-pig myenteric plexus and vas deferens. Toxicon 23 963-72. Arvidson, K.B., Valerio, L.G., Jr., Diaz, M., Chanderbhan, R.F. (2008). In silico toxicological screening of natural products. Toxicol. Mech. Meth. 18 229-42. 

Motilin is a neuropeptide expressed predominantly in the gastrointestinal tract that stimulates the contraction of gastrointestinal smooth muscle throughout the gut (Tonini 1996). Physiologically, its most characteristic role seems to be the induction of coordinated interdigestive antral and duodenal contractions (phase III of the migrating motor complex). The effects of motilin are both species and dose dependent. Motilin appears to have at least two receptors, one muscular and the other neuronal. Recent studies in vivo have emphasized the importance of the latter pathway and it is currently hypothesized that motilin acts on neurons in the myenteric plexus to release acetylcholine and other excitatory neurotransmitters. 

Fedotozine (Jo-1196,170), which is structurally related to the acyclic k agonists, has in vivo antinociceptive effects on duodenal pain that appear to be mediated by peripheral k opioid receptors, but the compound is inactive after central administration (544). In binding assays (in dog myenteric plexus), however, this compound exhibits similar affinity = 0.3-0.8 jM) for all three types of opioid receptors (545). Unlike other k agonists, fedotozine does not induce diuresis after either s.c. or in-tracerebroventricular (i.c.v.) administration (546). Fedotozine also fails to substitute for either U50,488 or morphine in animals trained to discriminate these drugs (547). The main effects demonstrated for fedotozine have been in the gastrointestinal tract (seeRef 548 for a detailed review of the pharmacology of fedotozine), and therefore this compound has... 

Roth SH (1978) Stereospecific presynaptic inhibitory effect of delta9-tetrahydrocannabinol on cholinergic transmission in the myenteric plexus of the guinea pig. Can J Physiol Pharmacol 56 968-975... 

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... 

Wessler 1, Dooley DJ, Werhand J, Schlemmer F. Differential effects of calcium channel antagonists (omega-conotoxin GVIA, nifedipine, verapamil) on the electrically-evoked release of [3H acetylcholine from the myenteric plexus, phrenic nerve and neocortex of rats. Naunyn Schmiedebergs Arch Pharmacol 1990 341(4) 288-94. 

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]. 

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