Neurons bearing NK 3 tachykinin receptors in the guinea-pig ileum revealed by specific binding of fluorescently labelled agonists

Jenkinson, Karl M; Morgan, Jan M.; Furness, John B.; Southwell, Bridget R.

doi:10.1007/s004180050411

Cited by 49 publications

(42 citation statements)

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“…We have utilized markers of all IPANs (IB4 and cytoplasmic NeuN) and have therefore analyzed a greater number of neurons. However, when our percentages are corrected for the difference in total neuron number, they are consistent with those reported previously (18).…”

Section: Discussionsupporting

confidence: 91%

“…This study indicated that 70 -80% of all myenteric neurons expressed NK 3 R, in accordance with electrophysiological investigations of senktide-responsive neurons (3). The functional subclasses of neurons with PKCε translocation are consistent with the previously reported distribution of the NK 3 R receptor in the guinea pig ileum (18). The number of IPANs with PKCε translocation in response to senktide is also consistent with the proportion of IPANs that express NK 3 R (18).…”

Section: Discussionsupporting

confidence: 88%

“…The distribution of the NK 3 R in the guinea pig ileum has been assayed by using a fluorescently labeled peptide agonist (18). This study indicated that 70 -80% of all myenteric neurons expressed NK 3 R, in accordance with electrophysiological investigations of senktide-responsive neurons (3).…”

Section: Discussionsupporting

confidence: 62%

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Stimulation of the neurokinin 3 receptor activates protein kinase Cε and protein kinase D in enteric neurons

Poole¹,

Amadesi²,

Thacker³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Poole DP, Amadesi S, Rozengurt E, Thacker M, Bunnett NW, Furness JB. Stimulation of the neurokinin 3 receptor activates protein kinase Cε and protein kinase D in enteric neurons. Am J Physiol Gastrointest Liver Physiol 294: G1245-G1256, 2008. First published February 28, 2008 doi:10.1152/ajpgi.00521.2007.-Tachykinins, acting through NK 3 receptors (NK3R), contribute to excitatory transmission to intrinsic primary afferent neurons (IPANs) of the small intestine. Although this transmission is dependent on protein kinase C (PKC), its maintenance could depend on protein kinase D (PKD), a downstream target of PKC. Here we show that PKD1/2-immunoreactivity occurred exclusively in IPANs of the guinea pig ileum, demonstrated by double staining with the IPAN marker NeuN. PKCε was also colocalized with PKD1/2 in IPANs. PKCε and PKD1/2 trafficking was studied in enteric neurons within whole mounts of the ileal wall. In untreated preparations, PKCε and PKD1/2 were cytosolic and no signal for activated (phosphorylated) PKD was detected. The NK 3R agonist senktide evoked a transient translocation of PKCε and PKD1/2 from the cytosol to the plasma membrane and induced PKD1/2 phosphorylation at the plasma membrane. PKCε translocation was maximal at 10 s and returned to the cytosol within 2 min. Phosphorylated-PKD1/2 was detected at the plasma membrane within 15 s and translocated to the cytosol by 2 min, where it remained active up to 30 min after NK3R stimulation. PKD1/2 activation was reduced by a PKCε inhibitor and prevented by NK3R inhibition. NK3R-mediated PKCε and PKD activation was confirmed in HEK293 cells transiently expressing NK3R and green fluorescent protein-tagged PKCε, PKD1, PKD2, or PKD3. Senktide caused membrane translocation and activation of kinases within 30 s. After 15 min, phosphorylated PKD had returned to the cytosol. PKD activation was confirmed through Western blotting. Thus stimulation of NK3R activates PKCε and PKD in sequence, and sequential activation of these kinases may account for rapid and prolonged modulation of IPAN function.tachykinins; primary afferent neurons THE THREE MAJOR TACHYKININ (neurokinin) receptors, NK 1 R, NK 2 R, and NK 3 R, are differentially expressed throughout the gastrointestinal tract. The principal endogenous tachykinins of enteric neurons are substance P and neurokinin A, neurokinin B being absent from enteric neurons (14). A major functional role of the NK 3 R in the gastrointestinal tract is to mediate noncholinergic slow excitatory postsynaptic potentials (sEPSPs) in myenteric intrinsic primary afferent neurons (IPANs) of the guinea pig ileum, thereby augmenting the excitability of these neurons (4). Similar transmission occurs in other regions of the gut, including the stomach, duodenum, and gallbladder (29, 42), suggesting a general functional role of NK 3 R in the enteric nervous system. Although NK 3 R has been shown to be involved in generating sEPSPs, NK 3 R antagonists fail to alter peristaltic contractions of the guinea pig small intestine (16). It has been s...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 88%

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Stimulation of the neurokinin 3 receptor activates protein kinase Cε and protein kinase D in enteric neurons

Poole¹,

Amadesi²,

Thacker³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…7), the non-cholinergic secretomotor neurons, in the guinea-pig ileum [51,82]. These neurons also exhibit slow EPSPs whose transmitter is unknown; because these neurons do not express NK 1 , NK 2 or NK 3 tachykinin receptors [53,73,101,102], it is unlikely to be a tachykinin. We have unpublished data indicating that slow EPSPs mediated by P2Y 1 receptors can also be seen in some myenteric S/uniaxonal neurons, (Fig.…”

Section: Slow Epsps Their Underlying Conductances and Their Transmitmentioning

confidence: 99%

Synaptic Transmission at Functionally Identified Synapses in the Enteric Nervous System: Roles for Both Ionotropic and Metabotropic Receptors

Gwynne

Bornstein²

2007

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Digestion and absorption of nutrients and the secretion and reabsorption of fluid in the gastrointestinal tract are regulated by neurons of the enteric nervous system (ENS), the extensive peripheral nerve network contained within the intestinal wall. The ENS is an important physiological model for the study of neural networks since it is both complex and accessible. At least 20 different neurochemically and functionally distinct classes of enteric neurons have been identified in the guinea pig ileum. These neurons express a wide range of ionotropic and metabotropic receptors. Synaptic potentials mediated by ionotropic receptors such as the nicotinic acetylcholine receptor, P2X purinoceptors and 5-HT 3 receptors are seen in many enteric neurons. However, prominent synaptic potentials mediated by metabotropic receptors, like the P2Y 1 receptor and the NK 1 receptor, are also seen in these neurons. Studies of synaptic transmission between the different neuron classes within the enteric neural pathways have shown that both ionotropic and metabotropic synaptic potentials play major roles at distinct synapses within simple reflex pathways. However, there are still functional synapses at which no known transmitter or receptor has been identified. This review describes the identified roles for both ionotropic and metabotropic neurotransmission at functionally defined synapses within the guinea pig ileum ENS. It is concluded that metabotropic synaptic potentials act as primary transmitters at some synapses. It is suggested identification of the interactions between different synaptic potentials in the production of complex behaviours will require the use of well validated computer models of the enteric neural circuitry.

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“…Tachykinins utilized as transmitters from enteric neurons target numerous enteric elements through NK1, NK2, or NK3 receptors. NK2 receptors occur primarily on muscle, whereas NK3 receptors are involved in neuroneuronal transmission (Johnson et al, 1996(Johnson et al, , 1998Portbury et al, 1996a;Jenkinson et al, 1999Jenkinson et al, , 2000Lecci et al, 2002). NK1 receptors have been shown acting on both muscle and enteric neurons.…”

Section: -Ht and Tachykinin In The Rabbit Ileummentioning

confidence: 99%

Interactions of Serotoninergic, Cholinergic, and Tachykinin‐Containing Nerve Elements in the Rabbit Small Intestine

Denes

Wilhelm

NÉMeth

et al. 2009

The Anatomical Record

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This report presents novel results on the effects of serotonin (5-HT) on longitudinal muscle contractions in the rabbit ileum and the interactions of serotonin with some neuronal elements of the myenteric plexus. We showed previously that serotonin-triggered contractions involved two mechanisms in the rabbit ileum: neuronal excitation (via 5-HT 2 receptors in the neurons) and direct muscular stimulation (via 5-HT 4 receptors in the muscle). Here, we focus on the neuronal 5-HT 2 receptor pathway and report further pharmacological and immunocytochemical data clarifying the details of the mechanisms. We observed that antagonists for neurokinin (NK1 and NK2) receptors partially blocked the serotonin response, but NK3 receptor antagonists had no effect. Pretreatment by atropine (ATR) eliminated the NK1 receptor antagonist resistant contractions. In contrast, the NK1 antagonist did not depress the ATR-resistant contraction when ATR was added first. 5-HT 2 receptor agonist-induced contractions were partially suppressed by ATR, hexamethonium, and NK1 or NK2 receptor antagonists. In conclusion, serotonin acting through 5-HT 2 receptors could stimulate interneurons and excitatory motor neurons. Immunocytochemical staining revealed an extensive tachykinin-immunoreactive (IR) network in the myenteric plexus. Approximately 52% of all myenteric neurons were labeled. 5-HT-IR fibers could be detected around both choline acetyltransferase-and tachykinin-IR cells, suggesting functional relationships between them. Consistent with our pharmacological observations, we found that immunopositive nerve elements for 5-HT 2A receptor and double-labeled immunostaining revealed a remarkable overlap between tachykinin-IR neurons and 5-HT 2A -IR elements. Anat Rec, 292:1548Rec, 292: -1558Rec, 292: , 2009. Key words: ileum; 5-HT; tachykinins; 5-HT 2 receptors; rabbit One of the principal regulators of digestion in mammals is the enteric nervous system. Enteric neurons coordinate a variety of functions, such as the secretion of digestive enzymes, control of absorption, and the regulation of motility. Intestinal smooth muscle contractility is organized by polarized reflex pathways through both excitatory and inhibitory neurons (Goyal and Hirano, 1996;Kunze and Furness, 1999;Olsson and Holmgren,

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Neurons bearing NK 3 tachykinin receptors in the guinea-pig ileum revealed by specific binding of fluorescently labelled agonists

Cited by 49 publications

References 54 publications

Stimulation of the neurokinin 3 receptor activates protein kinase Cε and protein kinase D in enteric neurons

Stimulation of the neurokinin 3 receptor activates protein kinase Cε and protein kinase D in enteric neurons

Synaptic Transmission at Functionally Identified Synapses in the Enteric Nervous System: Roles for Both Ionotropic and Metabotropic Receptors

Interactions of Serotoninergic, Cholinergic, and Tachykinin‐Containing Nerve Elements in the Rabbit Small Intestine

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