Activation of neurokinin 1 receptors on interstitial cells of Cajal of the guinea-pig small intestine by substance P

Lavin, S.; Southwell, Bridget R.; Murphy, Roger; Jenkinson, Karl M; Furness, John B.

doi:10.1007/s004180050288

Cited by 95 publications

(100 citation statements)

References 33 publications

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“…ICC express receptors for neurotransmitters such as neurokinins (NK1 and NK3 receptors), vasoactive intestinal polypeptide (VIP-1 receptors) and acetylcholine (muscarinic M 2 and M 3 receptors). 62,127,[191][192][193][194][195][196][197] Numerous studies have shown responses to NO in the GI tract depend upon the production of cyclic GMP (cGMP) by soluble guanylate cyclase. [198][199][200] Guanylate cyclase is a heterodimer comprised of 2 subunits, α and β.…”

Section: Functional Evidence Demonstrating the Importance Of Interstimentioning

confidence: 99%

“…[201][202][203] Furthermore, NK1 receptors are internalized in ICC in response to application of substance P and nerve stimulation, signifying that ICC are also targets for excitatory peptides. 61,62 Wang et al 204 found that protein kinase Cε (PKCε) translocates from the cytoplasm to the membrane of ICC-DMP in response to cholinergic stimulation, implying that a functional response to cholinergic stimulation also occurs in ICC. A more recent study showed that Ca 2+ -activated chloride channels are activated in ICC in response to cholinergic neurotransmission.…”

Section: Functional Evidence Demonstrating the Importance Of Interstimentioning

confidence: 99%

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The Significance of Interstitial Cells in Neurogastroenterology

Blair¹,

Rhee²,

Sanders³

et al. 2014

J Neurogastroenterol Motil

116

111

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Smooth muscle layers of the gastrointestinal tract consist of a heterogeneous population of cells that include enteric neurons, several classes of interstitial cells of mesenchymal origin, a variety of immune cells and smooth muscle cells (SMCs). Over the last number of years the complexity of the interactions between these cell types has begun to emerge. For example, interstitial cells, consisting of both interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor alpha-positive (PDGFRα + ) cells generate pacemaker activity throughout the gastrointestinal (GI) tract and also transduce enteric motor nerve signals and mechanosensitivity to adjacent SMCs. ICC and PDGFRα + cells are electrically coupled to SMCs possibly via gap junctions forming a multicellular functional syncytium termed the SIP syncytium. Cells that make up the SIP syncytium are highly specialized containing unique receptors, ion channels and intracellular signaling pathways that regulate the excitability of GI muscles. The unique role of these cells in coordinating GI motility is evident by the altered motility patterns in animal models where interstitial cell networks are disrupted. Although considerable advances have been made in recent years on our understanding of the roles of these cells within the SIP syncytium, the full physiological functions of these cells and the consequences of their disruption in GI muscles have not been clearly defined. This review gives a synopsis of the history of interstitial cell discovery and highlights recent advances in structural, molecular expression and functional roles of these cells in the GI tract.

show abstract

Section: Functional Evidence Demonstrating the Importance Of Interstimentioning

confidence: 99%

Section: Functional Evidence Demonstrating the Importance Of Interstimentioning

confidence: 99%

The Significance of Interstitial Cells in Neurogastroenterology

Blair¹,

Rhee²,

Sanders³

et al. 2014

J Neurogastroenterol Motil

116

111

View full text Add to dashboard Cite

show abstract

“…Excitatory motor neurons in the deep muscular plexus of the guinea pig small intestine (IC-DMP) appear to be as closely aligned with IC-DMP as inhibitory motor neurons (Wang et al, 1999). IC-DMP also express neurokinin 1 (NK1) receptors for tachykinins (Sternini et al, 1995;Grady et al, 1996;Young et al, 1996;Vannucchi et al, 1997), and when stimulated with fluorescently tagged substance-P, IC-DMP internalize NK1 receptors (Lavin et al, 1998). Thus, these cells express the structural and molecular components that would facilitate a role in excitatory neurotransmission.…”

mentioning

confidence: 99%

Interstitial Cells of Cajal Mediate Cholinergic Neurotransmission from Enteric Motor Neurons

et al. 2000

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Interstitial cells of Cajal (ICC) are interposed between enteric neurons and smooth muscle cells in gastrointestinal muscles. The role of intramuscular ICC (IC-IM) in mediating enteric excitatory neural inputs was studied using gastric fundus muscles of wild-type animals and W/W v mutant mice, which lack IC-IM. Excitatory motor neurons, labeled with antibodies to vesicular acetylcholine transporter or substance-P, were closely associated with IC-IM. Immunocytochemistry showed close contacts between enteric neurons and IC-IM. IC-IM also formed gap junctions with smooth muscle cells. Electrical field stimulation yielded fast excitatory junction potentials in the smooth muscle that were blocked by atropine. Neural responses were greatly reduced in muscles of W/W v animals. Loss of cholinergic responses in W/W v muscles seemed to be caused by the loss of close synaptic contacts between motor neurons and IC-IM, because these muscles were not less responsive to exogenous acetylcholine than were wild-type muscles. W/W v muscles also responded to excitatory nerve stimulation when the breakdown of acetylcholine was blocked by neostigmine. The density of cholinergic nerve bundles within the muscles was not significantly different in wild-type and W/W v muscles, and similar amounts of 14 [C]choline were released from preloaded wildtype and W/W v muscles in response to nerve stimulation. The impact of losing IC-IM on gastric compliance was also evaluated in intact stomachs. Pressure increased as a function of fluid volume and infusion rate in wild-type animals, but W/W v animals showed little basal tone and minimal increases in pressure with fluid infusions. These data suggest that IC-IM play a major role in receiving cholinergic excitatory inputs from the enteric nervous system in the murine fundus.

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“…Much of our knowledge about tachykinins in the gastrointestinal system is derived from extensive investigation in the guinea pig, where NK-1 receptors are prominent in contractile mechanisms (Holzer and Holzer-Petsche, 1997a,b) and have recently been identified on interstitial cells of Cajal (ICC), which have a pacemaker function (Lavin et al, 1998;Southwell and Furness, 2001). In contrast, in human colon, NK-2 receptors dominate the contraction of smooth muscle by tachykinins (Giuliani et al, 1991;Kölbel et al, 1994;Croci et al, 1998;Cao et al, 2000).…”

mentioning

confidence: 99%