Tachykinins mediate slow excitatory postsynaptic transmission in guinea pig sphincter of Oddi ganglia

Manning, Brian P.; Mawe, Gary M.

doi:10.1152/ajpgi.2001.281.2.g357

Cited by 14 publications

(5 citation statements)

References 35 publications

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“…Increasing the agonist application time did not change the time course of decay of the I Nav1.9 current because NK3r desensitizes and internalizes quickly (see below). In agreement with our results, slow depolarizations induced by substance P (SP) on neurons of ganglia of the sphincter of Oddi, were almost abolished when SP was applied 10 min after superfusion of the neurons with 1 μ m senktide (Manning & Mawe, 2001). Precise data on the early time course of NK3r desensitization and internalization are not available although in vivo experiments show that NK3r expressed by vasopressinergic neurons in the hypothalamic paraventricular nucleus are significantly internalized 5 min after senktide treatment (Haley & Flynn, 2007).…”

Section: Discussionsupporting

confidence: 90%

Activation of neurokinin 3 receptor increases Na_v1.9 current in enteric neurons

Copel

Osorio

Crest

et al. 2009

The Journal of Physiology

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The intrinsic primary afferent neurons (IPANs) of the guinea pig enteric nervous system express Na v 1.9 sodium channels that produce a persistent TTX-resistant current having a low activation threshold and slow gating kinetics. These neurons receive slow EPSPs induced mainly by the activation of neurokinin 3 receptors (NK3r). Here, we demonstrate that senktide, a specific NK3r agonist, potentiates the Na v 1.9 current (I Nav1.9 ) in IPANs. Using whole-cell patch-clamp recordings from IPANs in duodenum longitudinal muscle/myenteric plexus preparations, we show that short (1-5 s) and long (up to 1 min) applications of senktide, increase the I Nav1.9 peak current up to 13-fold. The effect, blocked by a NK3r antagonist SB235375 is transient, lasting ∼2 min and is due to a negative shift of the activation voltage by ∼20 mV and of fast inactivation by ∼10 mV. As a consequence, the window current resulting from the product of the activation and fast inactivation curves is shifted and enlarged. The transient effect of senktide is likely to be due to the fast desensitization of NK3r. Protein kinase C (PKC) activation with phorbol or oleoyl acetylglycerol also increases I Nav1.9 , although persistently, by inducing similar voltage-dependent changes. Current-clamp experiments showed that I Nav1.9 modulation by senktide lowers action potential threshold and increases excitability. The increase in I Nav1.9 by NK3r activation is also likely to amplify slow EPSPs generated in the IPANs. These changes in excitability potentially have a profound effect on the entire enteric synaptic circuit and ultimately on gut motility and secretion.

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Section: Discussionsupporting

confidence: 90%

Activation of neurokinin 3 receptor increases Na_v1.9 current in enteric neurons

Copel

Osorio

Crest

et al. 2009

The Journal of Physiology

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“…Although NK‐2 receptors are present predominantly on smooth muscle and, like NK‐1, can affect gut motility, 19 NK‐3 receptors are expressed predominantly in neurons and can stimulate or diminish muscle contraction indirectly following SP binding to neuronal cells in the submucosal and myenteric nerve plexuses of the gastrointestinal tract 20,21 . NK‐3 receptors also provide slow excitatory synaptic input to neurons in ganglia of the sphincter of Oddi 22 . Thus, both NK‐2 and NK‐3 receptors affect motility responses in the GI, but there is very little evidence that they are involved in neuroimmune interactions.…”

Section: Sp Receptors and Gut Distributionmentioning

confidence: 99%

Immunomodulatory Properties of Substance P

Koon

Pothoulakis

2006

Annals of the New York Academy of Sciences

124

112

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Communication between nerves and immune and inflammatory cells of the small and large intestine plays a major role in the modulation of several intestinal functions, including intestinal motility, ion transport, and mucosal permeability. Neuroimmune interactions at intestinal sites have been associated with the pathophysiology of infectious and enterotoxin-mediated diarrhea and intestinal inflammation, including inflammatory bowel disease (IBD). During the past 20 years the neuropeptide substance P (SP) has been identified as an important mediator in the development and progress of intestinal inflammation by binding to its high-affinity neurokinin-1 receptor (NK-1R). This peptide, released from enteric nerves, sensory neurons, and inflammatory cells of the lamina propria during intestinal inflammation, participates in gut inflammation by interacting, directly or indirectly, with NK-1R expressed on nerves, epithelial cells, and immune and inflammatory cells, such as mast cells, macrophages, and T cells. SP-dependent activation of these cells leads to the release of cytokines and chemokines as well as other neuropeptides that modulate diarrhea, inflammation, and motility associated with the pathophysiology of several intestinal disease states. The recent development of specific nonpeptide NK-1R antagonists and NK-1R-deficient mice helped us understand the functional importance of the SP-NK-1R system in mediating intestinal neuroimmune interactions and to identify the particular cells and signaling pathways involved in this response. This review summarizes our understanding on the immunomodulatory properties of SP and its receptor in the intestinal tract with particular focus on their involvement in intestinal physiology as well as in the pathophysiology of several intestinal disease states at the in vivo and cell signaling level.

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“…Large number of SP-positive nerve fibres associated with the SO have been also found in the cat (Feher et al 1995). Substance P and CGRP have appeared to have an excitatory effect on the opossum, guinea pig, canine and porcine SO (Guo et al 1989, Parodi et al 1989, Rasmussen et al 1997, Manning and Mawe 2001, and the effect of CGRP on the sphincter function involves cholinergic but not cholecystokininergic mechanisms (Rasmussen et al 1997).…”

Section: The Distribution and Chemical Coding Of Neuronsmentioning

confidence: 99%

The distribution and chemical coding of neurons supplying the sphincter of Oddi in mammals

Tomaszewska¹,

Kaleczyc²

2013

Polish Journal of Veterinary Sciences

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The major duodenal papilla (papilla of Vater) is an important structure associated with the biliary tract and, in some species, the pancreas. It usually represents a slight elevation on the intestinal mucosa where the dilated junction (ampulla of Vater) of the commmon bile duct and pancreatic duct enters the duodenum. The ampulla is surrounded by a specifically arranged muscle structure called the sphincter of Oddi (SO) which controls the flow of bile and pancreatic fluid. The function of the sphincter is regulated by a complex system that involves many hormonal and neural factors. The literature in the field contains detailed data on the morphology of the SO in a number of mammalian species. However, the comprehensive information about the anatomy and neurochemistry of the innervation of this structure is very limited. The present review article summarizes the current knowledge on the innervation of the SO in mammals. Special emphasis has been put on the localization and chemical coding of neurons contributing to this nerve supply.

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Tachykinins mediate slow excitatory postsynaptic transmission in guinea pig sphincter of Oddi ganglia

Cited by 14 publications

References 35 publications

Activation of neurokinin 3 receptor increases Na_v1.9 current in enteric neurons

Activation of neurokinin 3 receptor increases Na_v1.9 current in enteric neurons

Immunomodulatory Properties of Substance P

The distribution and chemical coding of neurons supplying the sphincter of Oddi in mammals

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Tachykinins mediate slow excitatory postsynaptic transmission in guinea pig sphincter of Oddi ganglia

Cited by 14 publications

References 35 publications

Activation of neurokinin 3 receptor increases Nav1.9 current in enteric neurons

Activation of neurokinin 3 receptor increases Nav1.9 current in enteric neurons

Immunomodulatory Properties of Substance P

The distribution and chemical coding of neurons supplying the sphincter of Oddi in mammals

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Product

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Activation of neurokinin 3 receptor increases Na_v1.9 current in enteric neurons

Activation of neurokinin 3 receptor increases Na_v1.9 current in enteric neurons